U.S. patent application number 11/813129 was filed with the patent office on 2009-03-05 for decaline-derived compounds as pharmaceutically active agents.
This patent application is currently assigned to UNIVERSITAT DORTMUND. Invention is credited to Marcus A. Koch, Alex Odermatt, Michael Scheck, Herbert Waldmann.
Application Number | 20090062401 11/813129 |
Document ID | / |
Family ID | 34928072 |
Filed Date | 2009-03-05 |
United States Patent
Application |
20090062401 |
Kind Code |
A1 |
Odermatt; Alex ; et
al. |
March 5, 2009 |
DECALINE-DERIVED COMPOUNDS AS PHARMACEUTICALLY ACTIVE AGENTS
Abstract
The present invention relates to compounds having a decaline
scaffold, pharmaceutically acceptable salts of these compounds and
pharmaceutical compositions containing at least one of these
compounds together with pharmaceutically acceptable carrier,
excipient and/or diluents. Said decaline-derived compounds can be
used for prophylaxsis and/or treatment of diabetes mellitus type I,
diabetes mellitus type II, tuberculosis and other infectious
diseases, proliferative diseases, cancer, neurodegenerative
diseases, obesity, cognitive dysfunctions and metabolic
syndromes.
Inventors: |
Odermatt; Alex; (Oberwil,
CH) ; Waldmann; Herbert; (Dortmund, DE) ;
Scheck; Michael; (Knittlingen, DE) ; Koch; Marcus
A.; (Dusseldorf, DE) |
Correspondence
Address: |
AMIN, TUROCY & CALVIN, LLP
127 Public Square, 57th Floor, Key Tower
CLEVELAND
OH
44114
US
|
Assignee: |
UNIVERSITAT DORTMUND
Dortmund
DE
MAX-PLANCK-GESELLSCHAFT ZUR FODERUNG DER WISSENSCHAFTEN
E.V.
Munich
DE
UNIVERSITAT BERN
Bern
DE
|
Family ID: |
34928072 |
Appl. No.: |
11/813129 |
Filed: |
December 28, 2005 |
PCT Filed: |
December 28, 2005 |
PCT NO: |
PCT/EP2005/014100 |
371 Date: |
September 25, 2008 |
Current U.S.
Class: |
514/681 ;
514/691; 568/327; 568/374 |
Current CPC
Class: |
A61P 5/44 20180101; A61P
9/00 20180101; A61P 25/28 20180101; C07C 69/732 20130101; A61P 3/00
20180101; A61P 31/00 20180101; C07C 69/716 20130101; C07C 49/753
20130101; C07C 215/44 20130101; C07C 49/747 20130101; A61P 17/02
20180101; A61P 5/00 20180101; C07C 217/54 20130101; A61P 3/10
20180101; A61P 31/06 20180101; C07C 49/743 20130101; C07C 35/36
20130101; C07C 205/45 20130101; A61P 3/04 20180101; C07C 2602/28
20170501; A61P 35/00 20180101 |
Class at
Publication: |
514/681 ;
568/374; 568/327; 514/691 |
International
Class: |
A61K 31/122 20060101
A61K031/122; C07C 49/733 20060101 C07C049/733; A61P 31/06 20060101
A61P031/06; A61P 3/10 20060101 A61P003/10; A61P 35/00 20060101
A61P035/00; A61P 25/28 20060101 A61P025/28; A61P 9/00 20060101
A61P009/00; A61P 5/44 20060101 A61P005/44; A61P 3/00 20060101
A61P003/00; A61P 17/02 20060101 A61P017/02; A61P 31/00 20060101
A61P031/00; A61P 3/04 20060101 A61P003/04; C07C 49/747 20060101
C07C049/747; C07C 49/743 20060101 C07C049/743 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 31, 2004 |
EP |
04031076.5 |
Claims
1. Compounds having the general formula (I): ##STR00047## wherein
the moiety ##STR00048## represents ##STR00049## R.sup.1 represents
hydrogen and R.sup.2 is --OH, --OR.sup.21, --NR.sup.14R.sup.15, or
R.sup.1 and R.sup.2 form together one of the residues .dbd.O,
.dbd.NR.sup.16, or .dbd.CR.sup.17R.sup.18; R.sup.3 and R.sup.4 are
hydrogen or form together the residue .dbd.CR.sup.19R.sup.20;
R.sup.5 and R.sup.6 represent independently of each other linear or
branched, substituted or unsubstituted C.sub.1-C.sub.6-alkyl,
linear or branched, substituted or unsubstituted
C.sub.2-C.sub.6-alkenyl, --H, -Ph, --CH.sub.2-Ph; R.sup.7
represents hydrogen and R.sup.8 is one of --OH, --OR.sup.21,
--NR.sup.22R.sup.23, or R.sup.7 and R.sup.8 form together the
residues .dbd.O; R.sup.9 and R.sup.10 are hydrogen or form together
the residue .dbd.CR.sup.24R.sup.25; R.sup.11, R.sup.12, R.sup.13
represent independently of each other --H, linear or branched,
substituted or unsubstituted C.sub.1-C.sub.6-alkyl, --CF.sub.3,
--CH.sub.2--CO--O-(linear or branched, substituted or unsubstituted
C.sub.1-C.sub.6-alkyl) or ##STR00050## R.sup.14 and R.sup.15
represent independently of each other --H, linear or branched,
substituted or unsubstituted C.sub.1-C.sub.6-alkyl, substituted or
unsubstituted C.sub.1-C.sub.10-cycloalkyl, or ##STR00051## R.sup.16
represents --H or linear or branched, substituted or unsubstituted
C.sub.1-C.sub.6-alkyl; R.sup.17 and R.sup.18 represent
independently of each other --H, linear or branched, substituted or
unsubstituted C.sub.1-C.sub.6-alkyl, --CO--O-(linear or branched,
substituted or unsubstituted C.sub.1-C.sub.6-alkyl), -Ph; R.sup.19
and R.sup.20 represent independently of each other --H, linear or
branched, substituted or unsubstituted C.sub.1-C.sub.20-alkyl,
substituted or unsubstituted heterocyclyl, substituted or
unsubstituted aryl, substituted or unsubstituted heteroaryl,
substituted or unsubstituted C.sub.1-C.sub.10-cycloalkyl
##STR00052## R.sup.21 represents --CF.sub.3, linear or branched,
substituted or unsubstituted C.sub.1-C.sub.20-alkyl; R.sup.22 and
R.sup.23 represent independently of each other --H, linear or
branched, substituted or unsubstituted C.sub.1-C.sub.20-alkyl,
substituted or unsubstituted C.sub.1-C.sub.10-cycloalkyl,
--CH.sub.2-Ph; R.sup.24 and R.sup.25 represent independently of
each other --H, substituted or unsubstituted aryl, substituted or
unsubstituted heteroaryl, linear or branched, substituted or
unsubstituted C.sub.1-C.sub.20-alkyl; R.sup.26-R.sup.38 represent
independently of each other linear or branched, substituted or
unsubstituted C.sub.1-C.sub.20-alkyl, --H, --OH, --OCH.sub.3,
--OC.sub.2H.sub.5, --OC.sub.3H.sub.7, --O-cyclo-C.sub.3H.sub.5,
--OCH(CH.sub.3).sub.2, --OC(CH.sub.3).sub.3, --OC.sub.4H.sub.9,
--OPh, --OCH.sub.2-Ph, --OCPh.sub.3, --SH, --SCH.sub.3,
--SC.sub.2H.sub.5, --SC.sub.3H.sub.7, --S-cyclo-C.sub.3H.sub.5,
--SCH(CH.sub.3).sub.2, --SC(CH.sub.3).sub.3, --NO.sub.2, --F, --Cl,
--Br, --I, --N.sub.3, --CN, --OCN, --NCO, --SCN, --NCS, --CHO,
--COCH.sub.3, --COC.sub.2H.sub.5, --COC.sub.3H.sub.7,
--CO-cyclo-C.sub.3H.sub.5, --COCH(CH.sub.3).sub.2,
--COC(CH.sub.3).sub.3, --COOH, --COCN, --COOCH.sub.3,
--COOC.sub.2H.sub.5, --COOC.sub.3H.sub.7,
--COO-cyclo-C.sub.3H.sub.5, --COOCH(CH.sub.3).sub.2,
--COOC(CH.sub.3).sub.3, --OOC--CH.sub.3, --OOC--C.sub.2H.sub.5,
--OOC--C.sub.3H.sub.7, --OOC-cyclo-C.sub.3H.sub.5,
--OOC--CH(CH.sub.3).sub.2, --OOC--C(CH.sub.3).sub.3, --CONH.sub.2,
--CONHCH.sub.3, --CONHC.sub.2H.sub.5, --CONHC.sub.3H.sub.7,
--CONH-cyclo-C.sub.3H.sub.5, --CONH[CH(CH.sub.3).sub.2],
--CONH[C(CH.sub.3).sub.3], --CON(CH.sub.3).sub.2,
--CON(C.sub.2H.sub.5).sub.2, --CON(C.sub.3H.sub.7).sub.2,
--CON(cyclo-C.sub.3H.sub.5).sub.2, --CON[CH(CH.sub.3).sub.2].sub.2,
--CON[C(CH.sub.3).sub.3].sub.2, --NH.sub.2, NHCH.sub.3,
--NHC.sub.2H.sub.5, --NHC.sub.3H.sub.7, --NH-cyclo-C.sub.3H.sub.5,
--NHCH(CH.sub.3).sub.2, --NHC(CH.sub.3).sub.3, --N(CH.sub.3).sub.2,
--N(C.sub.2H.sub.5).sub.2, --N(C.sub.3H.sub.7).sub.2,
--N(cyclo-C.sub.3H.sub.5).sub.2, --N[CH(CH.sub.3).sub.2].sub.2,
--N[C(CH.sub.3).sub.3].sub.2, --SOCH.sub.3, --SOC.sub.2H.sub.5,
--SOC.sub.3H.sub.7, --SO-cyclo-C.sub.3H.sub.5,
--SOCH(CH.sub.3).sub.2, --SOC(CH.sub.3).sub.3, --SO.sub.2CH.sub.3,
--SO.sub.2C.sub.2H.sub.5, --SO.sub.2C.sub.3H.sub.7,
--SO.sub.2-cyclo-C.sub.3H.sub.5, --SO.sub.2CH(CH.sub.3).sub.2,
--SO.sub.2C(CH.sub.3).sub.3, --SO.sub.3H, --SO.sub.3CH.sub.3,
--SO.sub.3C.sub.2H.sub.5, --SO.sub.3C.sub.3H.sub.7,
--SO.sub.3-cyclo-C.sub.3H.sub.5, --SO.sub.3CH(CH.sub.3).sub.2,
--SO.sub.3C(CH.sub.3).sub.3, --OCF.sub.3, --OC.sub.2F.sub.5,
--O--COOCH.sub.3, --O--COOC.sub.2H.sub.5, --O--COOC.sub.3H.sub.7,
--O--COO-cyclo-C.sub.3H.sub.5, --O--COOCH(CH.sub.3).sub.2,
--O--COOC(CH.sub.3).sub.3, --NH--CO--NH.sub.2,
--NH--CO--NHCH.sub.3, --NH--CO--NHC.sub.2H.sub.5,
--NH--CO--NHC.sub.3H.sub.7, --NH--CO--NH-cyclo-C.sub.3H.sub.5,
--NH--CO--NH[CH(CH.sub.3).sub.2], --NH--CO--NH[C(CH.sub.3).sub.3],
--NH--CO--N(CH.sub.3).sub.2, --NH--CO--N(C.sub.2H.sub.5).sub.2,
--NH--CO--N(C.sub.3H.sub.7).sub.2,
--NH--CO--N(cyclo-C.sub.3H.sub.5).sub.2,
--NH--CO--N[CH(CH.sub.3).sub.2].sub.2,
--NH--CO--N[C(CH.sub.3).sub.3].sub.2, --NH--CS--NH.sub.2,
--NH--CS--NH-cyclo-C.sub.3H.sub.5, --NH--CS--NHC.sub.3H.sub.7,
--NH--CS--NH[CH(CH.sub.3).sub.2], --NH--CS--NH[C(CH.sub.3).sub.3],
--NH--CS--N(CH.sub.3).sub.2, --NH--CS--N(C.sub.2H.sub.5).sub.2,
--NH--CS--N(C.sub.3H.sub.7).sub.2, --NH--CS--N
(cyclo-C.sub.3H.sub.5).sub.2,
--NH--CS--N[CH(CH.sub.3).sub.2].sub.2,
--NH--CS--N[C(CH.sub.3).sub.3].sub.2, --NH--C(.dbd.NH)--NH.sub.2,
--NH--C(.dbd.NH)--NHCH.sub.3, --NH--C(.dbd.NH)--NHC.sub.2H.sub.5,
--NH--CS--NHC.sub.2H.sub.5, --NH--C(.dbd.NH)--NHC.sub.3H.sub.7,
--NH--C(.dbd.NH)--NH-cyclo-C.sub.3H.sub.5,
--NH--C(.dbd.NH)--NH[CH(CH.sub.3).sub.2],
--NH--C(.dbd.NH)--NH[C(CH.sub.3).sub.3], --NH--CS--NHCH.sub.3,
--NH--C(.dbd.NH)--N(CH.sub.3).sub.2,
--NH--C(.dbd.NH)--N(C.sub.2H.sub.5).sub.2,
--NH--C(.dbd.NH)--N(C.sub.3H.sub.7).sub.2, --NH--C(.dbd.NH)--N
(cyclo-C.sub.3H.sub.5).sub.2,
--NH--C(.dbd.NH)--N[CH(CH.sub.3).sub.2].sub.2,
--NH--C(.dbd.NH)--N[C(CH.sub.3).sub.3].sub.2, --O--CO--NH.sub.2,
--O--CO--NHCH.sub.3, --O--CO--NHC.sub.2H.sub.5,
--O--CO--NHC.sub.3H.sub.7, --O--CO--NH-cyclo-C.sub.3H.sub.5,
--O--CO--NH[CH(CH.sub.3).sub.2], --O--CO--NH[C(CH.sub.3).sub.3],
--O--CO--N(CH.sub.3).sub.2, --O--CO--N(C.sub.2H.sub.5).sub.2,
--O--CO--N(C.sub.3H.sub.7).sub.2,
--O--CO--N(cyclo-C.sub.3H.sub.5).sub.2,
--O--CO--N[CH(CH.sub.3).sub.2].sub.2,
--O--CO--N[C(CH.sub.3).sub.3].sub.2, --O--CO--OCH.sub.3,
--O--CO--OC.sub.2H.sub.5, --O--CO--OC.sub.3H.sub.7,
--O--CO--O-cyclo-C.sub.3H.sub.5, --O--CO--OCH(CH.sub.3).sub.2,
--O--CO--OC(CH.sub.3).sub.3, --CH.sub.2F--CHF.sub.2, --CF.sub.3,
--CH.sub.2Cl, --CHCl.sub.2, --CCl.sub.3, --CH.sub.2Br --CHBr.sub.2,
--CBr.sub.3, --CH.sub.21--CH.sub.12, --Cl.sub.3, --CPh.sub.3,
--CH.sub.2--CH.sub.2F--CH.sub.2--CHF.sub.2, --CH.sub.2--CF.sub.3,
--CH.sub.2--CH.sub.2Cl, --CH.sub.2--CHCl.sub.2,
--CH.sub.2--CCl.sub.3, --CH.sub.2--CH.sub.2Br
--CH.sub.2--CHBr.sub.2, --CH.sub.2--CBr.sub.3,
--CH.sub.2--CH.sub.2I--CH.sub.2--CH 2, --CH.sub.2--Cl.sub.3,
--CH.sub.3, --C.sub.2H.sub.5, --C.sub.3H.sub.7,
-cyclo-C.sub.3H.sub.5, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3,
--C.sub.4H.sub.9, --CH.sub.2--CH(CH.sub.3).sub.2,
--CH(CH.sub.3)--C.sub.2H.sub.5, --C(CH.sub.3).sub.3, -Ph,
--CH.sub.2-Ph, --CH.dbd.CH.sub.2, --CH.sub.2--CH.dbd.CH.sub.2,
--C(CH.sub.3).dbd.CH.sub.2, --CH.dbd.CH--CH.sub.3,
--C.sub.2H.sub.4--CH.dbd.CH.sub.2, --CH.dbd.C(CH.sub.3).sub.2,
--C.ident.CH, --C.ident.C--CH.sub.3, --CH.sub.2--C.dbd.CH; R.sup.39
represents R.sup.37 or ##STR00053## and stereoisomeric forms,
prodrugs, solvates, hydrates and/or pharmaceutically acceptable
salts thereof.
2. Compound according to claim 1 having the general formula IIB,
##STR00054## wherein R.sup.5, R.sup.6, R.sup.9, R.sup.10, R.sup.29,
X and Z have the meanings as defined in claim 1.
3. Compound according to claim 1 or 2, wherein the compound is
selected from the group comprising:
(3E,4aS,5S)-3-(3,4-Difluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,-
4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Hydroxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-
-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Chlor-6-fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydrox-
y-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(Benzofuran-2-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydrox-
y-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3,4-bimethoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy--
1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3,4,5-Trimethoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Chlorobenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a--
dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4-
a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(4-Bromthiophen-2-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-[(pyridin-3--
yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Methylthio)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-
-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(4-Chlorthiophen-2-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-h-
ydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-[(1-methyl-1-
H-pyrrol-2-yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Hydroxy-4-methoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Ethyl-4-methoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Methoxy-2-methylbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hyd-
roxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Nitrobenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-Benzyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethyl-n-
aphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-[(4-methylth-
iophen-2-yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Methyl-4-octyl-benzyliden)-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Methylbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a--
dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-Dodecyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethyln-
aphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Ethyl-2-methylbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Methoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-
-dimethylnaphthalen-2(3H)-one,
(2E,8aS)-2-[(Furan-2-yl)methylen]-3,4,6,7,8,8a-hexahydro-6-hydroxy-5,8a-d-
imethylnaphthalen-1(2H)-one,
3-{(1E)-[(4S,4aS)-1,2,3,4,4a,5-Hexahydro-4-hydroxy-4a,8-dimethyl-7-oxonap-
hthalen-6(7H)-yliden]methyl}phenylacetat,
(3E,4aS,5S)-3-[(5-Bromthiophen-2-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2,4-Difluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,-
4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(E)-But-2-enyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a--
dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-[(thiophen-2-
-yl)methylen]naphthalen-2(3H)-one,
4-{(1E)-[(4S,4aS)-1,2,3,4,4a,5-Hexahydro-4-hydroxy-4a,8-dimethyl-7-oxonap-
hthalen-6(7H)-yliden]methyl}phenylacetat,
(3E,4aS,5S)-3-Butyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnap-
hthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimeth-yl-3-[(3-methylt-
hiophen-2-yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(Furan-2-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4-
a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-[(pyridin-4--
yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(2-Phenylethinyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(2-Methoxy-ethinyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5--
hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-tert-Butoxybut-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahy-
dro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(2-Cyclo-hexenylethinyl)benzyliden]-4,4a,5,6,7,8-hexahyd-
ro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Hex-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-
-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(2-p-Tolylethinyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-h-
ydroxy-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Nona-1,8-diinyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Hexadec-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hyd-
roxy-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-Hydroxy-3-methylbut-1-inyl)benzyliden]-4,4a,5,6,7,8-h-
exahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Dodec-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1,4a-dimethyl-naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3,3-Diethoxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahy-
dro-5-hydroxy-1,4a-dimethyl naphthalen-2(3H)-one,
6-{4-{(1E)-[(4S,4aS)-1,2,3,4,4a,5-Hexahydro-4-hydroxy-4a,8-dimethyl-7-oxo-
naphthalen-6(7H)-yliden]-methyl}phenyl}hex-5-in-nitril,
(3E,4aS,5S)-3-{4-[2-(1-Hydroxycyclohexyl)ethinyl]benzyliden}-4,4a,5,6,7,8-
-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[3-(N-Ethyl-N-benzylamino)prop-1-inyl]benzyliden}-4,4a,5-
,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[3-(Dimethylamino)prop-1-inyl]benzyliden}-4,4a,5,6,7,8-h-
exahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-Phenylprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro--
5-hydroxy-1,4a-dimethyl naphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(Trimethylsilyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexa-
hydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(17-Ethinyl-ostradiol)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(4-Hydroxybut-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro--
5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-Methylbut-3-en-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahy-
dro-5-hydroxy-1,4a-di methyl naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-Methyl
but-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaph-
thalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-3-{2-[(1S,3R,4S,5R)-1,3,4,5--
tetrahydroxycyclohexyl]-ethyliden}-1,4a-dimethyl
naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[3-(Furan-2-yl)propyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-
-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(E)-3-(Furan-2-yl)allyliden]-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2,3,4,5,6-Pentamethylbenzyliden)-4,4a,5,6,7,8-hexahydro-5--
hydroxy-1,4a-dimethyl naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4-
a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-di-
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-di-
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-di-
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Benzyloxy)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy--
1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dim-
ethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dim-
ethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dim-
ethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Brombutyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dim-
ethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-Methylbut-3-en-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahy-
dro-5-hydroxy-1,4a-dimethyl naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(5-Phenylpent-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro--
5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(2-Cyclohexyl-ethinyl)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-{4-[2-(1-Hydroxycyclohexyl)ethinyl]-benzyliden}-octahydro-5--
hydroxy-1,4a-dimethylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[4-(Octadec-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hyd-
roxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(9-Hydroxy-9H-fluoren-9-yl)ethinyl]benzyliden}-4,4a,5-
,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(1S,8aS)-6-(4-Iodphenylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylnap-
hthalen-1-ol,
(3E,4aS,5S)-3-[4-(2-Methoxy-4-nitrophenylamino)benzyliden]-4,4a,5,6,7,8-h-
exahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(4-Iodphenylamino)benzyliden]-4,4a,5,6,7,8-hexahydro-5-h-
ydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4-
a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-di-
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-(2-methylbut-
yliden)-naphthalen-2(3H)-one,
(E,4aS,5S)-3-(4-Chlorbenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphtha-
len-2(1H)-one,
(3E,4aS,5S)-3-(3-Fluor-4-methoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(3H)-one,
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-[(1-methyl-1H-pyrrol-2-yl)-
methylen]naphthalen-2(1H)-one,
(E,4aS,5S)-3-(3,4-Difluorbenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnap-
hthalen-2(1H)-one,
(E,4aS,5S)-3-(2-Chlor-6-fluorbenzyliden)-octahydro-5-hydroxy-1,4a-dimethy-
lnaphthalen-2(1H)-one,
(E,4aS,5S)-3-(4-Ethyl-2-methylbenzyliden)-octahydro-5-hydroxy-1,4a-dimeth-
ylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[4-(Undec-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Oct-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-
-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Tetradec-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(4-tert-Butylphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8--
hexahydro-5-hydroxy-1,4a-dimethyl naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3,3-Dimethylbut-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahyd-
ro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(1-Hydroxycyclopentyl)ethinyl]-benzyliden}-4,4a,5,6,7-
,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(1S,8aS)-1,2,3,4,6,7,8,8a-Octahydro-5,8a-dimethyl-6-methylennaphthalen-1--
ol,
(1S,7E,8aS)-7-Benzyliden-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethyl-6-me-
thylennaphthalen-1-ol,
(1S,7E,8aS)-1,2,3,4,6,7,8,8a-Octahydro-5,8a-dimethyl-6-methylen-7-pentyli-
dennaphthalen-1-ol, (2E)-Ethyl
2-[(4S,4aS)-2,3,4,4a,5,6-hexahydro-4-hydroxy-4a,8-dimethylnaphthalen-7(1H-
)-yliden]acetat,
(1S,6E,8aS)-6-Hexyliden-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylnaphthale-
n-1-ol,
(1S,6E,8aS)-6-Benzyliden-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethyln-
aphthalen-1-ol,
(1S,8aS)-5-(3,5-Dimethoxybenzyl)-decahydro-5,8a-dimethyl-6-methylennaphth-
alen-1-ol,
(E,4aS,5S)-3-(4-Hydroxy-3-methoxybenzyliden)-octahydro-5-hydrox-
y-1,4a-dimethylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[4-(3-Hydroxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(4-Chlorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-Phenylprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro--
5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2,3,4-Trihydroxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1,4a-dimethylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-(2,3,4-Trihydroxybenzyliden)-octahydro-5-hydroxy-1,4a-dimeth-
ylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-(2,3,4-Trihydroxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-4a-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2,3,4-Trihydroxybenzyliden)-4a-benzyl-4,4a,5,6,7,8-hexahyd-
ro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-3-[(R)-3-hydroxybutyliden]-1-
,4a-dimethylnaphthalen-2(3H)-one,
(E,4aS,5S)-Octahydro-5-hydroxy-3-[(R)-3-hydroxybutyliden]-1,4a-dimethylna-
phthalen-2(1H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-3-[(R)-3-hydroxybutyliden]-4-
a-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-3-[(R)-3-hydroxybu-
tyliden]-1-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(1H-Indol-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy--
1,4a-dimethylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-[(1H-Indol-3-yl)methylen]-octahydro-5-hydroxy-1,4a-dimethyln-
aphthalen-2(1H)-one,
(3E,4aS,5S)-3-[(1H-Indol-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy--
4a-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(1H-Indol-3-yl)methylen]-4a-benzyl-4,4a,5,6,7,8-hexahydro--
5-hydroxy-1-methylnaphthalen-2(3H)-one,
(E,5S,8aS)-2-[(1H-Indol-3-yl)methylen]-octahydro-6-hydroxy-5,8a-dimethyln-
aphthalen-1(2H)-one,
(3E,4aS,5S)-3-[(E)-But-2-enyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a--
dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(E)-But-2-enyliden]-octahydro-5-hydroxy-1,4a-dimethylnapht-
halen-2(1H)-one,
(3E,4aS,5S)-3-[(E)-But-2-enyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-me-
thylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-3-[(E)-but-2-enyliden]-4,4a,5,6,7,8-hexahydro-5-hyd-
roxy-1-methylnaphthalen-2(3H)-one,
(2E,8aS)-2-[(E)-But-2-enyliden]-octahydro-6-hydroxy-5,8a-dimethylnaphthal-
en-1(2H)-one,
(E,4aS,5S)-3-[4-(Oct-1-inyl)-benzyliden]-octahydro-5-hydroxy-1,4a-dimethy-
lnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[4-(Oct-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-[4-(Hexadec-1-inyl)benzyliden]-octahydro-5-hydroxy-1,4a-dime-
thylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[4-(Hexadec-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-[4-(Pent-1-inyl)benzyliden]-octahydro-5-hydroxy-1,4a-dimethy-
lnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[4-(Pent-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6,7,8-hexahydr-
o-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-[4-(Undec-1-inyl)benzyliden]-octahydro-5-hydroxy-1,4a-dimeth-
ylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[4-(Undec-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6,7,8-hexahyd-
ro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-[4-(Tetradec-1-inyl)benzyliden]-octahydro-5-hydroxy-1,4a-dim-
ethylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[4-(Tetradec-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6,7,8-hexa-
hydro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methyl-3-[(pyrid-
in-4-yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(2-Phenylethinyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-4a-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(Trimethylsilyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexa-
hydro-5-hydroxy-4a-methyl naphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(1-Hydroxycyclohexyl)ethinyl]benzyliden}-4,4a,5,6,7,8-
-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one,
(1S,8aS)-6-(Butylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylnaphthale-
n-1-ol,
(1S,8aS)-6-(Cyclohexylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimet-
hylnaphthalen-1-ol,
(1S,7E,8aS)-7-(4-Iodbenzyliden)-6-(cyclohexylamino)-1,2,3,4,6,7,8,8a-octa-
hydro-5,8a-dimethylnaphthalen-1-ol
(1S,8aS)-6-(4-Iodophenylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylna-
phthalen-1-ol,
(1S,8aS)-6-(4-Iodophenylamino)-5-benzyl-decahydro-5,8a-dimethylnaphthalen-
-1-ol,
(1S,8aS)-6-(2-Methoxy-4-nitrophenylamino)-1,2,3,4,6,7,8,8a-octahydr-
o-5,8a-dimethylnaphthalen-1-ol,
(1S,8aS)-5-(3,5-Dimethoxybenzyl)-6-(4-Iodophenylamino)-decahydro-5,8a-dim-
ethylnaphthalen-1-ol,
(1S,8aS)-5-(3,5-Dimethoxybenzyl)-6-(cyclohexylamino)-decahydro-5,8a-dimet-
hylnaphthalen-1-ol,
(1S,8aS)-5-(3,5-Dimethoxybenzyl)-6-(butylamino)-decahydro-5,8a-dimethylna-
phthalen-1-ol,
(1S,8aS)-7-(4-Iodbenzyl)-6-(butylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-d-
imethylnaphthalen-1-ol,
(4aS,5S)-3-[4-(3-tert-Butoxybut-1-inyl)benzyl]-4,4a,5,6,7,8-hexahydro-5-h-
ydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(4aS,5S)-3-{4-[3-(N-Benzyl-N-methylamino)prop-1-inyl]benzyl}-4,4a,5,6,7,8-
-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(4aS,5S)-{3-[4-(2-(Pyridin-2-yl)ethinyl]benzyl}-4,4a,5,6,7,8-hexahydro-5--
hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(4aS,5S)-3-[4-(4-Hydroxybut-1-inyl)benzyl]-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1,4a-dimethylnaphthalen-2(3H)-one,
Ethyl-2-[(4aS,5S)-decahydro-5-hydroxy-1,4a-dimethyl-2-oxonaphthalen-1-yl]-
acetat,
(3E,4aS,5S)-3-[(9-Ethyl-9H-carbazol-3-yl)methylen]-4,4a,5,6,7,8-he-
xahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(E,4aS,5S)-1-(3,5-Dimethoxy-benzyl)-3-(4-fluorbenzyliden)-octahydro-5-hyd-
roxy-1,4a-dimethylnaphthalen-2(1H)-one,
(E,4aS,5S)-3-(3,4-Dimethoxybenzyliden)-1-(3,5-dimethoxy-benzyl)-octahydro-
-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one,
(E,4aS,5S)-3-[(Benzofuran-2-yl)methylen]-octahydro-5-hydroxy-1,4a-dimethy-
lnaphthalen-2(1H)-one,
(3E,4aS,5S)-Octahydro-3-[(4,5-dihydro-3-methyl-1H-pyrrol-2-yl)methylen]-5-
-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5R)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-(perfluorben-
zyliden)naphthalen-2(3H)-one,
(E,4aS,5S)-3-(4-Brombenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphthal-
en-2(1H)-one,
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-[(1-methyl-1H-pyrrol-2-yl)-
methylen]naphthalen-2(1H)-one,
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-(2-methyl-butyliden)naphth-
alen-2(1H)-one,
(E,4aS,5S)-3-(4-Fluorbenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphtha-
len-2(1H)-one,
(3E,4R,4aS,5S)-3-(4-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a--
dimethylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(3-Chlorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4-
a-dimethylnaphthalen-2(3H)-one,
5-Hydroxy-1-methyl-7-phenyl-4,4a,5,6,7,8,-hexahydro-3H-naphthalen-2-one,
(3E,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-di-
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-di-
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-Ethyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnap-
hthalen-2(3H)-one,
(E,4aS,5S)-3-(2,3,4-Trimethoxy-benzyliden)-octahydro-5-hydroxy-1,4a-dimet-
hylnaphthalen-2(1H)-one,
(E,4aS,5S)-3-[4-(Methylthio)-benzyliden]-octahydro-5-hydroxy-1,4a-dimethy-
lnaphthalen-2(1H)-one,
(3E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-{[(S)-4-(prop-1-en-2-yl)c-
yclohex-1-enyl]-methylen}naphthalen-2(1H)-one,
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-[(5-methylfuran-2-yl)methy-
len]naphthalen-2(1H)-one,
(3E,4R,4aS,5S)-3-[2-(Benzyloxy)-benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-4,4a-dimethylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy--
4,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-di-
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-(2-methyl-bu-
tylidene)naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-(4-Iodbenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphthale-
n-2(1H)-one,
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-(2-methylbutyliden)naphtha-
len-2(1H)-one,
(E,4aS,5S)-3-(2-Iodbenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphthale-
n-2(1H)-one,
(E,4aS,5S)-3-(3-Chlorbenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphtha-
len-2(1H)-one,
(3E,4R,4aS,5S)-3-(2-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4-
a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(Furan-2-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a--
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2,3,4-Trimethoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(Methylthio)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-
-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-{[(S)-4-(pro-
p-1-en-2-yl)cyclohex-1-enyl]methylen}-naphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-[(5-methylfu-
ran-2-yl)methylen]naphthalen-2(3H)-one,
(E,4aS,5S)-3-[2-(Benzyloxy)-benzyliden]-octahydro-5-hydroxy-1,4a-dimethyl-
naphthalen-2(1H)-one,
(3E,4R,4aS,5S)-3-(3-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a--
dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dim-
ethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-(2-methyl-bu-
tyliden)naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dim-
ethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Chlorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-(2-Fluorbenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphtha-
len-2(1H)-one,
(3E,4R,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-4,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-meth-
ylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[2-(Benzyloxy)-benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy-
-1,4a-dimethyl naphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-[(2,6,6-trim-
ethylcyclohexa-1,3-dienyl)-methylen]naphthalen-2(3H)-one,
(E,4aS,5S)-3-(2,3,4,5,6-Pentamethylbenzyliden)-octahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(1H)-one,
(E,4aS,5S)-3-(3-Iodbenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphthale-
n-2(1H)-one,
(3E,4R,4aS,5S)-3-Benzyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-dimethy-
lnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-
-dimethylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(2-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-
-dimethylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-Ethyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-dimethyl-
naphthalen-2(3H)-one,
(E,4aS,5S)-3-(2,3,4-Trimethoxy-benzyliden)-octahydro-5-hydroxy-1,4a-dimet-
hylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-(2-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl-3-(2-methylpen-
tyliden)-naphthalen-2(3H)-one,
(E,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-octahydro-5-hydroxy-1,4a-dimeth-
ylnaphthalen-2(1H)-one,
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-(perfluorbenzyliden)naphth-
alen-2(1H)-one,
(3E,4R,4aS,5S)-3-(4-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-
-dimethylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(4-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4-
a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methy-
lnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2,3,4,5,6-Pentamethylbenzyliden)-4,4a,5,6,7,8-hexahydro-5--
hydroxy-1,4a-dimethyl naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dim-
ethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-(3-Brombenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphthal-
en-2(1H)-one,
(E,4aS,5S)-3-(2-Brombenzyliden)-octahydro-5-hydroxy-1,4a-dimethylnaphthal-
en-2(1H)-one,
(E,4aS,5S)-3-Ethyliden-octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)--
one,
(3E,4R,4aS,5S)-3-(2,3,4-Trimethoxybenzyliden)-4,4a,5,6,7,8-hexahydro--
5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-[4-(Methylthio)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-4,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[2-(Benzyloxy)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydroxy--
4a-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-met-
hylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-(2-methylpentyli-
den)naphthalen-2(3H)-one,
4-{(1E)-[(4S,4aS)-1,2,3,4,4a,5-Hexahydro-4-hydroxy-4a-methyl-7-oxonaphtha-
len-6(7H)-yliden]methyl}benzoic acid,
(3E,4aS,5S)-4a-Benzyl-3-[(furan-2-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-h-
ydroxy-1-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2,4,5-Trimethoxy-benzyliden)-4a-benzyl-4,4a,5,6,7,8-hexahy-
dro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methyl-3-(perflu-
orbenzyliden)naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(4-Brombenzyliden)-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hyd-
roxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-[(1-m-
ethyl-1H-pyrrol-2-yl)methylen]naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-(2-me-
thylbutylidene)-naphthalen-2(3H)-one, (E,
5S)-2-(4-Iodbenzyliden)-octahydro-6-hydroxy-5-methylnaphthalen-1(2H)-one,
(3E,4aS,5S)-3-(3-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methy-
lnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-met-
hylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-3-benzyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-met-
hylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Brombenzyliden)-4a-benzyl-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-1-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-3-ethyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-meth-
ylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(2,3,4-Trimethoxybenzyliden)-4a-allyl-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-[4-(Methylthio)-benzyliden]-4a-allyl-4,4a,5,6,7,8-hexahy-
dro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-{[(S)-
-4-(prop-1-en-2-yl)cyclohex-1-enyl]methylen}naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-[(5-m-
ethylfuran-2-yl)methylen]naphthalen-2(3H)-one,
(E,5S,8aS)-2-(2-(Benzyloxy)-benzyliden)-octahydro-6-hydroxy-5,8a-dimethyl-
naphthalen-1(2H)-one,
(3E,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydro-
xy-4a-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-(perfluorbenzyli-
den)naphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methyl-3-(2-meth-
ylbutyliden)naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Fluorbenzyliden)-4a-benzyl-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-1-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(4-Iodbenzyliden)-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-(2-me-
thylbutyliden)-naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(2-Iodbenzyliden)-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-4-methylnaphthalen-2(3H)-one,
(E,5S,8aS)-2-(2-Fluorbenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphtha-
len-1(2H)-one,
(3E,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-meth-
ylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-Ethyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphtha-
len-2(3H)-one,
(3E,4aS,5S)-3-(2,3,4-Trimethoxybenzyliden)-4a-benzyl-4,4a,5,6,7,8-hexahyd-
ro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-[2-(Benzyloxy)-benzyliden]-4a-allyl-4,4a,5,6,7,8-hexahyd-
ro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-{[(R)-
-4-(prop-1-en-2-yl)cyclohex-1-enyl]-methylen}naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-3-[(furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-
-hydroxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-[(2,6-
,6-trimethyl-cyclohexa-1,3-dienyl)methylen]-naphthalen-2(3H)-one,
(E,
5S,8aS)-2-(2,3,4,5,6-Pentamethyl-benzyliden)-octahydro-6-hydroxy-5,8a-dim-
ethylnaphthalen-1(2H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-[(1-methyl-1H-py-
rrol-2-yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-(2-methylbutylid-
en)naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(4-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-met-
hylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methyl-3-(2-meth-
ylbutyliden)naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(2-Fluorbenzyliden)-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-(2-me-
thylpentyliden)-naphthalen-2(3H)-one, (E,
5S,8aS)-2-[(Furan-2-yl)methylen]-octahydro-6-hydroxy-5,8a-dimethylnaphtha-
len-1(2H)-one, (E,
5S,8aS)-2-(2,4,5-Trimethoxy-benzyliden)-octahydro-6-hydroxy-5,8a-dimethyl-
naphthalen-1(2H)-one,
(3E,4aS,5S)-3-[4-(Methylthio)-benzyliden]-4,4a,5,6,7,8-hexahydro-5-hydrox-
y-4a-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-{[(S)-4-(prop-1--
en-2-yl)cyclohex-1-enyl]methylen}naphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-[(5-methylfuran--
2-yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-[(5-methylfuran--
2-yl)methylen]naphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methyl-3-{[(S)-4-
-(prop-1-en-2-yl)cyclohex-1-enyl]methylen}naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(2,3,4,5,6-Pentamethylbenzyliden)-4a-allyl-4,4a,5,6,7,8--
hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(3-Iodbenzyliden)-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(3-Fluorbenzyliden)-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hy-
droxy-4-methylnaphthalen-2(3H)-one, (E,
5S,8aS)-2-(3-Brombenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphthalen--
1(2H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-(2-met-
hylbutyliden)naphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methy-
lnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(2-Fluorbenzyliden)-4a-benzyl-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-1-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methyl-3-(2-meth-
ylpentyliden)naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-4a-allyl-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-propy-
lidennaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methyl-3-(perf-
luorbenzyliden)-naphthalen-2(3H)-one, (E,
5S,8aS)-2-(4-Brombenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphthalen--
1(2H)-one, (E,
5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-[(1-methyl-1H-pyrrol-2-yl)met-
hylen]naphthalen-1(2H)-one,
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-{[(R)-4-(prop-1--
en-2-yl)cyclohex-1-enyl]methylen}naphthalen-2(3H)-one,
(3E,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a--
methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-(3-Fluorbenzyliden)-4a-benzyl-4,4a,5,6,7,8-hexahydro-5-hydr-
oxy-1-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-4a-Allyl-3-benzyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-m-
ethylnaphthalen-2(3H)-one,
(E,5S,8aS)-2-(2,3,4-Trimethoxy-benzyliden)-octahydro-6-hydroxy-5,8a-dimet-
hylnaphthalen-1(2H)-one,
(E,5S,8aS)-2-(4-(Methylthio)-benzyliden)-octahydro-6-hydroxy-5,8a-dimethy-
lnaphthalen-1(2H)-one,
(E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-(2-methylbutyliden)naphtha-
len-1(2H)-one,
(E,5S,8aS)-2-(2-Iodbenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphthale-
n-1(2H)-one,
(E,5S,8aS)-2-(3-Chlorbenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphtha-
len-1(2H)-one,
(2E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-{[(S)-4-(prop-1-en-2-yl)c-
yclohex-1-enyl]methylen}naphthalen-1(2H)-one, (E,
5S,8aS)-2-[(Furan-2-yl)methylen]-octahydro-6-hydroxy-5,8a-dimethylnaphtha-
len-1(2H)-one,
(2E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-[(2,6,6-trimethylcyclohex-
a-1,3-dienyl)-methylen]naphthalen-1(2H)-one, (E,
5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-(2-methyl-pentyliden)naphthal-
en-1(2H)-one,
4-{(E)-[(1S,4aS)-Octahydro-2-hydroxy-1,4a-dimethyl-5-oxonaphthalen-6(1H)--
yliden]methyl}benzoic acid,
(E,5S,8aS)-2-(3-Iodbenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphthale-
n-1(2H)-one,
(E,5S,8aS)-2-(3-Fluorbenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphtha-
len-1(2H)-one, (E,
5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-propyliden-naphthalen-1(2H)-o-
ne, (E,
5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-(perfluorbenzyliden)na-
phthalen-1(2H)-one, (E,
5S,8aS)-2-(2-Brombenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphthalen--
1(2H)-one,
(E,5S,8aS)-2-Ethyliden-octahydro-6-hydroxy-5,8a-dimethylnaphtha-
len-1(2H)-one, (E,
5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-(2-methylbutyliden)naphthalen-
-1(2H)-one, (E,
5S,8aS)-2-(4-Fluorbenzyliden)-octahydro-6-hydroxy-5,8a-dimethylnaphthalen-
-1(2H)-one,
(2E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-{[(R)-4-(prop-1-en-2-yl)c-
yclohex-1-enyl]-methylen}naphthalen-1(2H)-one, (E,
5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-[(5-methylfuran-2-yl)methylen-
]naphthalen-1(2H)-one, (E,
11S,8aS)-7-[2-(2-Cyclohexylethinyl)benzyliden]-6-(butylamino)-decahydro-5-
,8a-dimethylnaphthalen-1-ol,
(E,4aS)-6-[2-(Hexadec-1-inyl)benzyliden]-5-(butylamino)-decahydro-1,4a-di-
methylnaphthalen-2-ol,
(1S,7E,8aS)-7-{2-[2-(Trimethylsilyl)ethinyl]benzyliden}-6-(butylamino)-1,-
213,4,6,7,8,8a-octahydro-5,8a-dimethylnaphthalen-1-ol,
(E,1S,8aS)-7-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-6-(butylamino)-deca-
hydro-5,8a-dimethylnaphthalen-1-ol,
(1S,7E,8aS)-7-[2-(3-Methoxyprop-1-inyl)benzyliden]-6-(butyl-amino)-1,2,3,-
4,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol,
(1S,7E,8aS)-7-{2-[2-(Trimethylsilyl)ethyl]-benzyliden}-6-(butylamino)-1,2-
,3,4,6,7,8,8a-octahydro-5,8a-dimethylnaphthalen-1-ol,
(1S,7E,8aS)-7-[2-(2-Cyclohexylethinyl)benzyliden]-6-(butyl-amino)-1,2,3,4-
,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol,
(E,4aS)-6-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-5-(butylamino)-decahyd-
ro-1,4a-dimethylnaphthalen-2-ol,
(1S,7E,8aS)-7-[2-(2-Cyclohexylethinyl)benzyliden]-6-(butylamino)-1,2,3,4,-
6,7,8,8a-octahydro-5,8a-dimethylnaphthalen-1-ol,
(E,1S,8aS)-7-[2-(3-Methoxyprop-1-inyl)benzyliden]-6-(butylamino)-decahydr-
o-5,8a-dimethylnaphthalen-1-ol,
(E,4aS)-6-{2-[3-(Dimethylamino)prop-1-inyl]benzyliden}-5-(butylamino)-dec-
ahydro-1,4a-dimethylnaphthalen-2-ol,
(1S,7E,8aS)-7-[2-(Hex-1-inyl)-benzyliden]-6-(cyclohexyl-amino)-1,2,3,4,6,-
7,8,8a-octahydro-5,8a-dimethylnaphthalen-1-ol,
(1S,7E,8aS)-7-{2-[3-(Dimethylamino)prop-1-inyl]benzyliden}-6-(cyclohexyla-
mino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylnaphthalen-1-ol,
(E,4aS)-6-[2-(Oct-1-inyl)benzyliden]-5-(cyclohexylamino)-decahydro-1,4a-d-
imethylnaphthalen-2-ol,
(1S,7E,8aS)-7-{2-[3-(Dimethylamino)prop-1-inyl]benzyliden}-8a-benzyl-6-(c-
yclohexylamino)-1,2,3,4,6,7,8,8a-octahydro-5-methylnaphthalen-1-ol,
(3E,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-4a-methyl naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-[2-(Hexadec-1-inyl)benzyliden]-4a-allyl-4,4a,5,6,7,8-hex-
ahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]-octahydro-5-hydroxy-1,4-
a-dimethylnaphthalen-2(1H)-one,
(E,8aS)-2-{2-[3-(Dimethylamino)prop-1-inyl]benzyliden}-octahydro-6-hydrox-
y-5,8a-dimethylnaphthalen-1(2H)-one,
(3E,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-1,4a-dimethyl naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahy-
dro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-octahydro-5-hydroxy-
-1,4a-dimethylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[2-(Hexadec-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hyd-
roxy-4a-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4a-allyl-4,4a,5-
,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-4a-methyl naphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-he-
xahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one,
(E,8aS)-2-[2-(Hex-1-inyl)benzyliden]-octahydro-6-hydroxy-5,8a-dimethylnap-
hthalen-1(2H)-one,
(3E,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6,7,8-
-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(1S,6E,7E,8S,8aS)-7-[3-(2-Cyclohexylethinyl)benzyliden]-8a-allyl-6-(butyl-
imino)-1,2,3,4,6,7,8,8a-octahydro-8-methylnaphthalen-1-ol,
(E,4aS)-6-[3-(3-Methoxyprop-1-inyl)benzyliden]-5-(butylamino)-decahydro-1-
,4a-dimethylnaphthalen-2-ol,
(E,4aS)-6-[3-(3-Hydroxy-3-methylbut-1-inyl)benzyliden]-5-(butylamino)-dec-
ahydro-1,4a-dimethylnaphthalen-2-ol,
(1S,7E,8aS)-7-[3-(2-Cyclohexylethinyl)benzyliden]-6-(butyl-amino)-1,2,3,4-
,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol,
(E,4aS)-6-{3-[2-(2-Fluorphenyl)ethinyl]benzyliden}-5-(butylamino)-decahyd-
ro-1,4a-dimethylnaphthalen-2-ol,
(E,4aS)-6-[3-(Hex-1-inyl)benzyliden]-5-(butylamino)-decahydro-1,4a-dimeth-
ylnaphthalen-2-ol,
(E,1S,8aS)-7-[3-(3-Methoxyprop-1-inyl)benzyliden]-6-(butylamino)-decahydr-
o-5,8a-dimethylnaphthalen-1-ol,
(E,1S,8aS)-7-[3-(3-Methoxyprop-1-inyl)benzyliden]-6-(cyclohexylamino)-dec-
ahydro-5,8a-dimethylnaphthalen-1-ol,
(E,1S,8S,8aR)-7-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-8a-allyl-6-(cycl-
ohexylamino)-decahydro-5,8-dimethylnaphthalen-1-ol,
(3E,4aS,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one,
(E,4R,4aR,5S)-3-[3-(3-Methoxyprop-1-inyl)benzyliden]-4a-allyl-octahydro-5-
-hydroxy-1,4-dimethylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(E,8aS)-2-[3-(3-Methoxyprop-1-inyl)benzyliden]-octahydro-6-hydroxy-5,8a-d-
imethylnaphthalen-1(2H)-one,
(E,4aS,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-octahydro-5-hydroxy-
-1,4a-dimethylnaphthalen-2(1H)-one,
(E,4R,4aR,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4a-allyl-octahyd-
ro-5-hydroxy-1,4-dimethylnaphthalen-2(1H)-one,
(3E,4aS,5S)-3-[3-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-4a-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[3-(Hexadec-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-5-hyd-
roxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-he-
xahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[3-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[3-(3-Methoxyprop-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6,7,8-
-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(E,1S,8aS)-7-[3-(3-Methoxyprop-1-inyl)benzyliden]-6-(butylamino)-decahydr-
o-5,8a-dimethylnaphthalen-1-ol,
(E,1S,8aS)-7-[3-(2-Cyclohexylethinyl)benzyliden]-6-(butylamino)-decahydro-
-5,8a-dimethylnaphthalen-1-ol,
(E,4aS)-6-[3-(3-Methoxyprop-1-inyl)benzyliden]-5-(butylamino)-decahydro-1-
,4a-dimethylnaphthalen-2-ol,
(E,1S,8S,8aR)-7-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-8a-allyl-6-(buty-
lamino)-decahydro-5,8-dimethylnaphthalen-1-ol,
(E,4aS)-6-[3-(3-Hydroxy-3-methylbut-1-inyl)benzyliden]-5-(butylamino)-dec-
ahydro-1,4a-dimethylnaphthalen-2-ol,
(1S,7E,8aS)-7-[3-(2-Cyclohexylethinyl)benzyliden]-6-(butyl-amino)-1,2,3,4-
,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol,
(E,4aS)-6-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-5-(butylamino)-decahyd-
ro-1,4a-dimethylnaphthalen-2-ol,
(1S,7E,8aS)-7-[3-(3-Hydroxy-3-methylbut-1-inyl)benzyliden]-6-(butylamino)-
-1,2,3,4,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol, (E,
1S,8S,8aR)-7-[3-(3-Methoxyprop-1-inyl)benzyliden]-8a-allyl-6-(butylamino)-
-decahydro-5,8-dimethylnaphthalen-1-ol,
(E,4aS)-6-{3-[3-(Dimethylamino)prop-1-inyl]benzyliden}-5-(butylamino)-dec-
ahydro-1,4a-dimethylnaphthalen-2-ol,
(E,4aS)-6-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-5-(cyclohexylamino)-de-
cahydro-1,4a-dimethylnaphthalen-2-ol,
(1S,7E,8aS)-7-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-8a-benzyl-6-(cyclo-
hexylamino)-1,2,3,4,6,7,8,8a-octahydro-5-methylnaphthalen-1-ol,
(E,4aS)-6-[3-(3-Methoxyprop-1-inyl)benzyliden]-5-(cyclohexylamino)-decahy-
dro-1,4a-dimethylnaphthalen-2-ol,
(E,4aS)-6-[3-(2-Cyclohexylethinyl)benzyliden]-5-(cyclohexylamino)-decahyd-
ro-1,4a-dimethylnaphthalen-2-ol, (E,4aS)-6-[3-(3-Methyl
but-3-en-1-inyl)benzyliden]-5-(cyclohexylamino)-decahydro-1,4a-dimethylna-
phthalen-2-ol,
(3E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-4a-methyl naphthalen-2(3H)-one,
(E,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-octahydro-5-hydroxy-1,4-
a-dimethylnaphthalen-2(1H)-one,
(3E,4R,4aS,5S)-3-{4-[3-(Dimethylamino)prop-1-inyl]benzyliden}-4,4a,5,6,7,-
8-hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-4a-allyl-4,4a,5,6,7-
,8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5,6,7,8-hexah-
ydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4a-benzyl-4,4a,5,6-
,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-[4-(2-Cyclohexylethinyl)benzyliden]-4a-allyl-4,4a,5,6,7,-
8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one,
(E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}-octahydro-5-hydroxy-
-1,4a-dimethylnaphthalen-2(1H)-one,
(3E,4R,4aS,5S)-3-[4-(3-Cyclohexylprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hex-
ahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-4a-methylnaphthalen-2(3H)-one,
(E,8aS)-2-{4-[2-(3-Fluorphenyl)-ethinyl]benzyliden}-octahydro-6-hydroxy-5-
,8a-dimethylnaphthalen-1(2H)-one,
(3E,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6,7,8-hexahydro-
-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one,
(3E,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6,7,8-
-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one,
(3E,4R,4aS,5S)-3-{4-[3-(Dimethylamino)
prop-1-inyl]benzyliden}-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methy-
lnaphthalen-2(3H)-one,
(1S,8aS)-6-(Diethylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylnaphtha-
len-1-ol,
(1S,8S,8aS)-6-(Diethylamino)-1,2,3,4,6,7,8,8a-octahydro-8,8a-dim-
ethylnaphthalen-1-ol,
(1S,8aS)-6-(Diethylamino)-1,2,3,4,6,7,8,8a-octahydro-8a-methylnaphthalen--
1-ol,
(1S,8aR)-8a-Benzyl-6-(diethylamino)-1,2,3,4,6,7,8,8a-octahydro-5-met-
hylnaphthalen-1-ol,
(1S,8S,8aS)-8a-Allyl-6-(diethylamino)-1,2,3,4,6,7,8,8a-octahydro-8-methyl-
naphthalen-1-ol,
(6E,4aS)-2-Furan-2-ylmethylene-5,8a-dimethyl-6-methylene-3,4,6,7,8,8a-hex-
ahydro-2H-naphthalen-1-one,
2-Furan-2-ylmethylene-8-methyl-3,4,4a,5,8,8a-hexahydro-2H-naphthalen-1-on-
e,
(4aS,5S)-5-Hydroxy-1,4a-dimethyl-3-(4-pyridin-4-ylethynyl-benzylidene)--
4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-one,
(4aS,5S)-3-[4-(3-Dimethylamino-prop-1-ynyl)-benzylidene]-5-hydroxy-1,4a-d-
imethyl-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-one,
(4aS,5S)-5-Hydroxy-1,4a-dimethyl-1-(3-phenyl-propyl)-octahydro-naphthalen-
-2-one,
(4aS,5S)-5-Hydroxy-1-(3-iodo-benzyl)-1,4a-dimethyl-octahydro-napht-
halen-2-one,
(4aS,5S)-3-(4-Cyclohexylamino-benzylidene)-5-hydroxy-1,4a-dimethyl-4,4a,5-
,6,7,8-hexahydro-3H-naphthalen-2-one,
(4aS)-5,8a-Dimethyl-7-(5-methyl-furan-2-ylmethylene)-hexahydro-naphthalen-
-1,6-dione,
(2E,4aS)-5-(1,4a-Dimethyl-5-oxo-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-yl-
idene)-5H-furan-2-one,
(7'E)-7'-(4-iodo-benzylidene)-5',8a'-dimethyl
hexahydro-5'-(2-phenylethyl)-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-6'(-
5'H)-one,
2-Furan-2-ylmethylene-3,4,4a,5,8,8a-hexahydro-2H-naphthalen-1-on-
e,
(4aS)-7-Benzylidene-5,8a-dimethyl-hexahydro-naphthalen-1,6-dione,
(4aS,5S)-5-Hydroxy-1,4a-dimethyl-1-(2-nitro-benzyl)-octahydro-naphthalen--
2-one,
(4aS,5S)-5-Hydroxy-1-isobutyl-1,4a-dimethyl-1-octahydro-naphthalen--
2-one, 8-Methyl-3,4,4a,5,8,8a-hexahydro-2H-naphthalen-1-one,
(3E,4aS)-5,8a-Dimethyl-7-(2,4,6-trimethoxy-benzylidene)-3,4,8,8a-tetrahyd-
ro-2H,7H-naphthalen-1,6-dione,
(3E,3'E,4aS,4a'S)-1,3-bis[5,8a-dimethyl-3,4,8,8a-tetrahydro-2H,7H-naphtha-
len-1,6-dione]-benzene,
(4aS)-5-Butyliminomethyl-8a-methyl-3,4,8,8a-tetrahydro-2H,7H-naphthalen-1-
,6-dione,
(2E,4aS,5S)-6-Ethylidene-5,8a-dimethyl-1,2,3,4,6,7,8,8a-octahydr-
o-naphthalen-1-ol,
(4aS,5S)-5-Hydroxy-3-[1-(4-iodo-phenyl)-propyl]-1,4a-dimethyl-4,4a,5,6,7,-
8-hexahydro-3H-naphthalen-2-one,
(4aS,5S)-5-Hydroxy-1,4a-dimethyl-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-o-
ne,
(4aS,5S)-1-Butyl-5-hydroxy-1,4a-dimethyl-1-octahydro-naphthalen-2-one,
(5E)-5-(5', 8a'-dimethyl-3',4',
8',8a'-tetrahydro-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-6'(7'H)-yliden-
e)furan-2(5H)-one,
(7'E)-5'-(3,5-Dibromobenzyl)-7'-(4-iodo-benzylidene)-5',
8a'-dimethylhexahydro-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-6'(5'H)-on-
e,
5-Hydroxy-7-isopropyl-1-methyl-4,4a,5,6,7,8,-hexahydro-3H-naphthalen-2--
one,
(4aS,5S)-5-Hydroxy-1,4a-dimethyl-1-octahydro-naphthalen-2-one.
4. Compound according to any previous claim for use as a
pharmaceutically active agent.
5. Use of a compound according to any one of claims 1-4 as an
inhibitor for at least one enzyme selected from the group
comprising Cdc25A, AChE, 11.beta.HSD1, 11.beta.HSD2, MtPTPA, PP1,
VHR, PTP1B.
6. Use of a compound according to any one of claims 1-4 for
prophylaxis and treatment of diseases associated with the enzymes
Cdc25A, AChE, 11.beta.HSD1, 11.beta.HSD2, MtPTPA, PP1, VHR, PTP1B
or curable by inhibition of at least one of the enzymes Cdc25A,
AChE, 11.beta.HSD1, or 11.beta.HSD2, MtPTPA, PP1, VHR, PTP1B.
7. Use of a compound according to any one of claims 1-4 for
prophylaxis and treatment of diabetes mellitus type I, diabetes
mellitus type II, tuberculosis, proliferative diseases, cancer,
infectious diseases, neurodegenerative diseases, obesity, cognitive
dysfunctions, wound healing, cardiovascular diseases and disorders,
glucocorticoid dysfunction and metabolic syndromes or as
angiogenesis inhibitor.
8. Use according to claim 7, where the neurodegenerative disease is
selected from the group comprising: Alzheimer disease, Parkinson
disease, Huntington disease, amyotrophic lateral sclerosis,
AIDS-related dementia, retinitis pigmentosa, spinal muscular
atrophy and cerebrellar degeneration, fragile X-associated
tremor/ataxia syndrome (FXTAS), progressive supranuclear palsy
(PSP), and striatonigral degeneration (SND), which is included with
olivopontocerebellear degeneration (OPCD), and Shy Drager syndrome
(SDS) in a syndrome known as multiple system atrophy (MSA).
9. Use according to claim 7, wherein the proliferative disease or
cancer is selected from the group comprising: adenocarcinoma,
choroidal melanoma, acute leukemia, acoustic neurinoma, ampullary
carcinoma, anal carcinoma, astrocytoma, basal cell carcinoma,
pancreatic cancer, desmoid tumor, bladder cancer, bronchial
carcinoma, breast cancer, Burkitt's lymphoma, corpus cancer,
CUP-syndrome (carcinoma of unknown primary), colorectal cancer,
small intestine cancer, small intestinal tumors, ovarian cancer,
endometrial carcinoma, ependymoma, epithelial cancer types, Ewing's
tumors, gastrointestinal tumors, gastric cancer, gallbladder
cancer, gall bladder carcinomas, uterine cancer, cervical cancer,
cervix, glioblastomas, gynecologic tumors, ear, nose and throat
tumors, hematologic neoplasias, hairy cell leukemia, urethral
cancer, skin cancer, skin testis cancer, brain tumors (gliomas),
brain metastases, testicle cancer, hypophysis tumor, carcinoids,
Kaposi's sarcoma, laryngeal cancer, germ cell tumor, bone cancer,
colorectal carcinoma, head and neck tumors (tumors of the ear, nose
and throat area), colon carcinoma, craniopharyngiomas, oral cancer
(cancer in the mouth area and on lips), cancer of the central
nervous system, liver cancer, liver metastases, leukemia, eyelid
tumor, lung cancer, lymph node cancer (Hodgkin's/Non-Hodgkin's),
lymphomas, stomach cancer, malignant melanoma, malignant neoplasia,
malignant tumors gastrointestinal tract, breast carcinoma, rectal
cancer, medulloblastomas, melanoma, meningiomas, Hodgkin's disease,
mycosis fungoides, nasal cancer, neurinoma, neuroblastoma, kidney
cancer, renal cell carcinomas, non-Hodgkin's lymphomas,
oligodendroglioma, esophageal carcinoma, osteolytic carcinomas and
osteoplastic carcinomas, osteosarcomas, ovarial carcinoma,
pancreatic carcinoma, penile cancer, plasmocytoma, prostate cancer,
pharyngeal cancer, rectal carcinoma, retinoblastoma, vaginal
cancer, thyroid carcinoma, Schneeberger disease, esophageal cancer,
spinalioms, T-cell lymphoma (mycosis fungoides), thymoma, tube
carcinoma, eye tumors, urethral cancer, urologic tumors, urothelial
carcinoma, vulva cancer, wart appearance, soft tissue tumors, soft
tissue sarcoma, Wilm's tumor, cervical carcinoma and tongue
cancer.
10. Use according to claim 7, wherein the infectious disease
including opportunistic infection is selected from the group
comprising: AIDS, Alveolar Hydatid Disease (AHD, Echinococcosis),
Amebiasis (Entamoeba histolytica Infection), Angiostrongylus
Infection, Anisakiasis, Anthrax, Babesiosis (Babesia Infection),
Balantidium Infection (Balantidiasis), Baylisascaris Infection
(Raccoon Roundworm), Bilharzia (Schistosomiasis), Blastocystis
hominis Infection (Blastomycosis), Boreliosis, Botulism, Brainerd
Diarrhea, Brucellosis, BSE (Bovine Spongiform Encephalopathy),
Candidiasis, Capillariasis (Capillaria Infection), CFS (Chronic
Fatigue Syndrome), Chagas Disease (American Trypanosomiasis),
Chickenpox (Varicella-Zoster virus), Chlamydia pneumoniae
Infection, Cholera, Chronic Fatigue Syndrome, CJD
(Creutzfeldt-Jakob Disease), Clonorchiasis (Clonorchis Infection),
CLM (Cutaneous Larva Migrans, Hookworm Infection),
Coccidioidomycosis, Conjunctivitis, Coxsackievirus A16 (Hand, Foot
and Mouth Disease), Cryptococcosis, Cryptosporidium Infection
(Cryptosporidiosis), Culex mosquito (Vector of West Nile Virus),
Cutaneous Larva Migrans (CLM), Cyclosporiasis (Cyclospora
Infection), Cysticercosis (Neurocysticercosis), Cytomegalovirus
Infection, Dengue/Dengue Fever, Ebola Virus Hemorrhagic Fever,
Echinococcosis (Alveolar Hydatid Disease), Encephalitis, Entomoeba
coli Infection, Entomoeba dispar Infection, Entomoeba hartmanni
Infection, Entomoeba histolytica Infection (Amebiasis), Entomoeba
polecki Infection, Enterobiasis (Pinworm Infection), Enterovirus
Infection (Non-Polio), Epstein-Barr Virus Infection, Escherichia
coli Infection, Foodborne Infection, Foot and mouth Disease, Fungal
Dermatitis, Gastroenteritis, Group A streptococcal Disease, Group B
streptococcal Disease, Hansen's Disease (Leprosy), Hantavirus
Pulmonary Syndrome, Helicobacter pylori Infection, Hematologic
Disease, Hendra Virus Infection, Hepatitis (HCV, HBV), Herpes
Zoster (Shingles), HIV Infection, Human Ehrlichiosis, Human
Parainfluenza Virus Infection, Influenza, Isosporiasis (Isospora
Infection), Lassa Fever, Leishmaniasis, Kala-azar (Kala-azar,
Leishmania Infection), Leprosy, Lice (Body lice, Head lice, Pubic
lice), Lyme Disease, Malaria, Marburg Hemorrhagic Fever, Measles,
Meningitis, Mosquito-borne Diseases, Mycobacterium avium Complex
(MAC) Infection, Naegleria Infection, Nosocomial Infections,
Nonpathogenic Intestinal Amebae Infection, Onchocerciasis (River
Blindness), Opisthorciasis (Opisthorcis Infection), Parvovirus
Infection, Plague, PCP (Pneumocystis carinii Pneumonia), Polio, Q
Fever, Rabies, Respiratory Syncytial Virus (RSV) Infection,
Rheumatic Fever, Rift Valley Fever, River Blindness
(Onchocerciasis), Rotavirus Infection, Roundworms Infection,
Salmonellosis, Salmonella Enteritidis, Scabies, Shigellosis,
Shingles, Sleeping Sickness, Smallpox, Streptococcal Infection,
Tapeworm Infection (Taenia Infection), Tetanus, Toxic Shock
Syndrome, Tuberculosis, Ulcers (Peptic Ulcer Disease), Valley
Fever, Vibrio parahaemolyticus Infection, Vibrio vulnificus
Infection, Viral Hemorrhagic Fever, Warts, Waterborne infectious
Diseases, West Nile Virus Infection (West Nile Encephalitis),
Whooping Cough, Yellow Fever, tuberculosis, leprosy,
mycobacteria-induced meningitis.
11. Use according to claim 7, where the cognitive disorder is
selected from the group comprising anxiety disorders, delirium,
dementia, amnestic disorders, dissociative disorders, eating
disorders, mood disorders, schizophrenia, psychotic disorders,
sexual and gender identity disorders, sleep disorders, somatoform
disorders, acute stress disorder, obsessive-compulsive disorder,
panic disorder, posttraumatic stress disorder, specific phobia,
social phobia, substance withdrawal delirium, Alzheimer's disease,
Creutzfeldt-Jakob disease, head trauma, Huntington's disease, HIV
disease, Parkinson's disease, Pick's disease, learning disorders,
motor skills disorders, developmental coordination disorder,
communication disorders, phonological disorder, pervasive
developmental disorders, Asperger's disorder, autistic disorder,
childhood disintegrative disorder, Rett's disorder, pervasive
developmental disorder, attention-deficit/hyperactivity disorder
(ADHD), conduct disorder, oppositional defiant disorder, pica,
rumination disorder, tic disorders, chronic motor or vocal tic
disorder, Tourette's disorder, elimination disorders, encopresis,
enuresis, selective mutism, separation anxiety disorder,
dissociative amnesia, depersonalization disorder, dissociative
fugue, dissociative identity disorder, anorexia nervosa, bulimia
nervosa, bipolar disorders, schizophreniform disorder,
schizoaffective disorder, delusional disorder, psychotic disorder,
shared psychotic disorder, delusions, hallucinations,
substance-induced psychotic disorder, orgasmic disorders, sexual
pain disorders, dyspareunia, vaginismus, sexual dysfunction,
paraphilias, dyssomnias, breathing-related sleep disorder,
circadian rhythm sleep disorder, hypersomnia, insomnia, narcolepsy,
dyssomnia, parasomnias, nightmare disorder, sleep terror disorder,
sleepwalking disorder, parasomnia, body dysmorphic disorder,
conversion disorder, hypochondriasis, pain disorder, somatization
disorder, alcohol related disorders, amphetamine related disorders,
caffeine related disorders, cannabis related disorders, cocaine
related disorders, hallucinogen related disorders, inhalant related
disorders, nicotine related disorders, opioid related disorders,
phencyclidine-related disorder, abuse, persisting amnestic
disorder, intoxication, withdrawal.
12. Use according to claim 7, where the cardiovascular disease,
cardiovascular disorder, glucocorticoid dysfunction or metabolic
syndrome is selected from the group comprising metabolic syndrome,
visceral obesity, insulin resistance, dyslipidemia, obesity,
impaired glucose tolerance, hypertriglyceridemia, Cushing's
syndrome, Addison's disease, glucocorticoid hypersensitivity,
glucocorticoid resistance, hypercortisolism, the dysmetabolic
syndrome, diabetes type 2, melancholic depression, osteoporosis,
anxiety, insomnia, asthenia, depression, memory dysfunction,
executive dysfunction, fatigue, hyperalgesia, poor quality sleep,
insulin resistance, atrophy (sarcopenia), growth stunting, adult
congenital heart disease, aneurysm, stable angina, unstable angina,
angina pectoris, angioneurotic edema, aortic valve stenosis, aortic
aneurysm, arrhythmia, arrhythmogenic right ventricular dysplasia,
arteriosclerosis, atherosclerosis, arteriovenous malformations,
atrial fibrillation, Behcet syndrome, bradycardia, cardiac
tamponade, cardiomegaly, congestive cardiomyopathy, hypertrophic
cardiomyopathy, restrictive cardiomyopathy, cardiovascular disease
prevention, carotid stenosis, cerebral hemorrhage, Churg-Strauss
syndrome, Ebstein's Anomaly, Eisenmenger complex, cholesterol
embolism, bacterial endocarditis, fibromuscular dysplasia,
congenital heart defects, heart diseases, congestive heart failure,
heart valve diseases, heart attack, epidural hematoma, hematoma,
subdural, Hippel-Lindau disease, hyperemia, hypertension, pulmonary
hypertension, hypertrophic growth, left ventricular hypertrophy,
right ventricular hypertrophy, hypoplastic left heart syndrome,
hypotension, intermittent claudication, ischemic heart disease,
Klippel-Trenaunay-Weber syndrome, lateral medullary syndrome, long
QT syndrome mitral valve prolapse, moyamoya disease, mucocutaneous
lymph node syndrome, myocardial infarction, myocardial ischemia,
myocarditis, pericarditis, peripheral vascular diseases, phlebitis,
polyarteritis nodosa, pulmonary atresia, Raynaud disease,
restenosis, Sneddon syndrome, stenosis, superior vena cava
syndrome, syndrome X, tachycardia, Takayasu's arteritis, hereditary
hemorrhagic telangiectasia, telangiectasis, temporal arteritis,
tetralogy of fallot, thromboangiitis obliterans, thrombosis,
thromboembolism, tricuspid atresia, varicose veins, vascular
diseases, vasculitis, vasospasm, ventricular fibrillation, Williams
syndrome, peripheral vascular disease, varicose veins and leg
ulcers, deep vein thrombosis, Wolff-Parkinson-White syndrome.
13. Use of a compound according to any one of claims 1-4 in
combination with an anti-HIV drug, antiproliferative drug,
cytotoxic or cytostatic drug, ganciclovir, foscarnet, cidofovir,
valganciclovir, fomivirsen, penciclovir or valaciclovir.
14. Pharmaceutical composition comprising at least one compound
according to any one of claims 1 to 4 as an active ingredient,
together with at least one pharmaceutically acceptable carrier,
excipient and/or diluents.
Description
[0001] The present invention relates to compounds having a decaline
scaffold, and stereoisomeric forms, prodrugs, solvates, hydrates
and/or pharmaceutically acceptable salts of these compounds as well
as pharmaceutical compositions containing at least one of these
decaline derivatives together with pharmaceutically acceptable
carrier, excipient and/or diluents. Said decaline-derived compounds
are useful for prophylaxsis and/or treatment of diabetes mellitus
type I, diabetes mellitus type II, tuberculosis and other
infectious diseases, proliferative diseases, cancer,
neurodegenerative diseases, obesity, cognitive dysfunctions and
metabolic syndromes.
BACKGROUND OF THE INVENTION
[0002] U.S. Pat. No. 6,482,851 B1 discloses dysidiolide compounds
and a process for the preparation of said compounds. Furthermore,
it is stated that these compounds show an inhibitory effect on the
positive cell cycle regulator Cdc25 and the kinases Cdk4, Cdk2 and
Cdc2. Said dysidiolide compounds exhibit the potential to act as
anti-cancer drugs, since the growth of a number of human tumor cell
lines was inhibited with IC.sub.50 values ranging from 0.5 to 4.5
.mu.M.
[0003] It is object of the present invention to provide compounds
and/or pharmaceutically acceptable salts thereof which can be used
as pharmaceutically active agents, especially for prophylaxis
and/or treatment of diabetes mellitus type I, diabetes mellitus
type II, tuberculosis and other infectious diseases, proliferative
diseases, cancer, neurodegenerative diseases, obesity, cognitive
dysfunctions and metabolic syndromes, as well as compositions
comprising at least one of those compounds and/or pharmaceutically
acceptable salts thereof as pharmaceutically active
ingredients.
[0004] The object of the present invention is solved by the
teaching of the independent claims. Further advantageous features,
aspects and details of the invention are evident from the dependent
claims, the description, and the examples of the present
application.
[0005] The novel decaline derivatives according to the present
invention are represented by the following general formula (I)
##STR00001##
wherein the moiety
##STR00002##
represents
##STR00003##
R.sup.1 represents hydrogen and R.sup.2 is --OH, --OR.sup.21,
--NR.sup.14R.sup.15, or R.sup.1 and R.sup.2 form together one of
the residues .dbd.O, .dbd.NR.sup.16, or .dbd.CR.sup.17R.sup.18;
R.sup.3 and R.sup.4 are hydrogen or form together the residue
.dbd.CR.sup.19R.sup.20; R.sup.5 and R.sup.6 represent independently
of each other linear or branched, substituted or unsubstituted
C.sub.1-C.sub.6-alkyl, linear or branched, substituted or
unsubstituted C.sub.2-C.sub.6-alkenyl, --H, -Ph, --CH.sub.2-Ph;
R.sup.7 represents hydrogen and R.sup.8 is one of --OH,
--OR.sup.21, --NR.sup.22R.sup.23, or R.sup.7 and R.sup.8 form
together the residues .dbd.O; R.sup.9 and R.sup.10 are hydrogen or
form together the residue .dbd.CR.sup.24R.sup.25; R.sup.11,
R.sup.12, R.sup.13 represent independently of each other --H,
linear or branched, substituted or unsubstituted
C.sub.1-C.sub.6-alkyl, --CF.sub.3, --CH.sub.2--CO--O-(linear or
branched, substituted or unsubstituted C.sub.1-C.sub.6-alkyl)
or
##STR00004##
R.sup.14 and R.sup.15 represent independently of each other --H,
linear or branched, substituted or unsubstituted
C.sub.1-C.sub.6-alkyl, substituted or unsubstituted
C.sub.1-C.sub.10-cycloalkyl, or
##STR00005##
R.sup.16 represents --H or linear or branched, substituted or
unsubstituted C.sub.1-C.sub.6-alkyl; R.sup.17 and R.sup.18
represent independently of each other --H, linear or branched,
substituted or unsubstituted C.sub.1-C.sub.6-alkyl, --CO--O-(linear
or branched, substituted or unsubstituted C.sub.1-C.sub.6-alkyl),
-Ph; R.sup.19 and R.sup.20 represent independently of each other
--H, linear or branched, substituted or unsubstituted
C.sub.1-C.sub.20-alkyl, substituted or unsubstituted heterocyclyl,
substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, substituted or unsubstituted
C.sub.1-C.sub.10-cycloalkyl
##STR00006##
R.sup.21 represents --CF.sub.3, linear or branched, substituted or
unsubstituted C.sub.1-C.sub.20-alkyl; R.sup.22 and R.sup.23
represent independently of each other --H, linear or branched,
substituted or unsubstituted C.sub.1-C.sub.20-alkyl, substituted or
unsubstituted C.sub.1-C.sub.10-cycloalkyl, --CH.sub.2-Ph; R.sup.24
and R.sup.25 represent independently of each other --H, substituted
or unsubstituted aryl, substituted or unsubstituted heteroaryl,
linear or branched, substituted or unsubstituted
C.sub.1-C.sub.20-alkyl; R.sup.26-- R.sup.38 represent independently
of each other linear or branched, substituted or unsubstituted
C.sub.1-C.sub.20-alkyl, --H, --OH, --OCH.sub.3, --OC.sub.2H.sub.5,
--OC.sub.3H.sub.7, --O-cyclo-C.sub.3H.sub.5, --OCH(CH.sub.3).sub.2,
--OC(CH.sub.3).sub.3, --OC.sub.4H.sub.9, --OPh, --OCH.sub.2-Ph,
--OCPh.sub.3, --SH, --SCH.sub.3, --SC.sub.2H.sub.5,
--SC.sub.3H.sub.7, --S-cyclo-C.sub.3H.sub.5, --SCH(CH.sub.3).sub.2,
--SC(CH.sub.3).sub.3, --NO.sub.2, --F, --Cl, --Br, --I, --N.sub.3,
--CN, --OCN, --NCO, --SCN, --NCS, --CHO, --COCH.sub.3,
--COC.sub.2H.sub.5, --COC.sub.3H.sub.7, --CO-cyclo-C.sub.3H.sub.5,
--COCH(CH.sub.3).sub.2, --COC(CH.sub.3).sub.3, --COOH, --COCN,
--COOCH.sub.3, --COOC.sub.2H.sub.5, --COOC.sub.3H.sub.7,
--COO-cyclo-C.sub.3H.sub.5, --COOCH(CH.sub.3).sub.2,
--COOC(CH.sub.3).sub.3, --OOC--CH.sub.3, --OOC--C.sub.2H.sub.5,
--OOC--C.sub.3H.sub.7, --OOC-cyclo-C.sub.3H.sub.5,
--OOC--CH(CH.sub.3).sub.2, --OOC--C(CH.sub.3).sub.3, --CONH.sub.2,
--CONHCH.sub.3, --CONHC.sub.2H.sub.5, --CONHC.sub.3H.sub.7,
--CONH-cyclo-C.sub.3H.sub.5, --CONH[CH(CH.sub.3).sub.2],
--CONH[C(CH.sub.3).sub.3], --CON(CH.sub.3).sub.2,
--CON(C.sub.2H.sub.5).sub.2, --CON(C.sub.3H.sub.7).sub.2,
--CON(cyclo-C.sub.3H.sub.5).sub.2, --CON[CH(CH.sub.3).sub.2].sub.2,
--CON[C(CH.sub.3).sub.3].sub.2, --NH.sub.2, --NHCH.sub.3,
--NHC.sub.2H.sub.5, --NHC.sub.3H.sub.7, --NH-cyclo-C.sub.3H.sub.5,
--NHCH(CH.sub.3).sub.2, --NHC(CH.sub.3).sub.3, --N(CH.sub.3).sub.2,
--N(C.sub.2H.sub.5).sub.2, --N(C.sub.3H.sub.7).sub.2, --N
(cyclo-C.sub.3H.sub.5).sub.2, --N[CH(CH.sub.3).sub.2].sub.2,
--N[C(CH.sub.3).sub.3].sub.2, --SOCH.sub.3, --SOC.sub.2H.sub.5,
--SOC.sub.3H.sub.7, --SO-cyclo-C.sub.3H.sub.5,
--SOCH(CH.sub.3).sub.2, --SOC(CH.sub.3).sub.3, --SO.sub.2CH.sub.3,
--SO.sub.2C.sub.2H.sub.5, --SO.sub.2C.sub.3H.sub.7,
--SO.sub.2-cyclo-C.sub.3H.sub.5, --SO.sub.2CH(CH.sub.3).sub.2,
--SO.sub.2C(CH.sub.3).sub.3, --SO.sub.3H, --SO.sub.3CH.sub.3,
--SO.sub.3C.sub.2H.sub.5, --SO.sub.3C.sub.3H.sub.7,
--SO.sub.3-cyclo-C.sub.3H.sub.5, --SO.sub.3CH(CH.sub.3).sub.2,
--SO.sub.3C(CH.sub.3).sub.3, --OCF.sub.3, --OC.sub.2F.sub.5,
--O--COOCH.sub.3, --O--COOC.sub.2H.sub.5, --O--COOC.sub.3H.sub.7,
--O--COO-cyclo-C.sub.3H.sub.5, --O--COOCH(CH.sub.3).sub.2,
--O--COOC(CH.sub.3).sub.3, --NH--CO--NH.sub.2,
--NH--CO--NHCH.sub.3, --NH--CO--NHC.sub.2H.sub.5,
--NH--CO--NHC.sub.3H.sub.7, --NH--CO--NH-cyclo-C.sub.3H.sub.5,
--NH--CO--NH[CH(CH.sub.3).sub.2], --NH--CO--NH[C(CH.sub.3).sub.3],
--NH--CO--N(CH.sub.3).sub.2, --NH--CO--N(C.sub.2H.sub.5).sub.2,
--NH--CO--N(C.sub.3H.sub.7).sub.2,
--NH--CO--N(cyclo-C.sub.3H.sub.5).sub.2,
--NH--CO--N[CH(CH.sub.3).sub.2].sub.2,
--NH--CO--N[C(CH.sub.3).sub.3].sub.2, --NH--CS--NH.sub.2,
--NH--CS--NH-cyclo-C.sub.3H.sub.5, --NH--CS--NHC.sub.3H.sub.7,
--NH--CS--NH[CH(CH.sub.3).sub.2], --NH--CS--NH[C(CH.sub.3).sub.3],
--NH--CS--N(CH.sub.3).sub.2, --NH--CS--N(C.sub.2H.sub.5).sub.2,
--NH--CS--N(C.sub.3H.sub.7).sub.2,
--NH--CS--N(cyclo-C.sub.3H.sub.5).sub.2,
--NH--CS--N[CH(CH.sub.3).sub.2].sub.2,
--NH--CS--N[C(CH.sub.3).sub.3].sub.2, --NH--C(.dbd.NH)--NH.sub.2,
--NH--C(.dbd.NH)--NHCH.sub.3, --NH--C(.dbd.NH)--NHC.sub.2H.sub.5,
--NH--CS--NHC.sub.2H.sub.5, --NH--C(.dbd.NH)--NHC.sub.3H.sub.7,
--NH--C(.dbd.NH)--NH-cyclo-C.sub.3H.sub.5,
--NH--C(.dbd.NH)--NH[CH(CH.sub.3).sub.2],
--NH--C(.dbd.NH)--NH[C(CH.sub.3).sub.3], --NH--CS--NHCH.sub.3,
--NH--C(.dbd.NH)--N(CH.sub.3).sub.2,
--NH--C(.dbd.NH)--N(C.sub.2H.sub.5).sub.2,
--NH--C(.dbd.NH)--N(C.sub.3H.sub.7).sub.2,
--NH--C(.dbd.NH)--N(cyclo-C.sub.3H.sub.5).sub.2,
--NH--C(.dbd.NH)--N[CH(CH.sub.3).sub.2].sub.2,
--NH--C(.dbd.NH)--N[C(CH.sub.3).sub.3].sub.2, --O--CO--NH.sub.2,
--O--CO--NHCH.sub.3, --O--CO--NHC.sub.2H.sub.5,
--O--CO--NHC.sub.3H.sub.7, --O--CO--NH-cyclo-C.sub.3H.sub.5,
--O--CO--NH[CH(CH.sub.3).sub.2], --O--CO--NH[C(CH.sub.3).sub.3],
--O--CO--N(CH.sub.3).sub.2, --O--CO--N(C.sub.2H.sub.5).sub.2,
--O--CO--N(C.sub.3H.sub.7).sub.2,
--O--CO--N(cyclo-C.sub.3H.sub.5).sub.2,
--O--CO--N[CH(CH.sub.3).sub.2].sub.2,
--O--CO--N[C(CH.sub.3).sub.3].sub.2, --O--CO--OCH.sub.3,
--O--CO--OC.sub.2H.sub.5, --O--CO--OC.sub.3H.sub.7,
--O--CO--O-cyclo-C.sub.3H.sub.5, --O--CO--OCH(CH.sub.3).sub.2,
--O--CO--OC(CH.sub.3).sub.3, --CH.sub.2F--CHF.sub.2, --CF.sub.3,
--CH.sub.2Cl, --CHCl.sub.2, --CCl.sub.3, --CH.sub.2Br --CHBr.sub.2,
--CBr.sub.3, --CH.sub.21--CH.sub.12, --Cl.sub.3,
--CH.sub.2--CH.sub.2F--CH.sub.2--CHF.sub.2, --CH.sub.2--CF.sub.3,
--CH.sub.2--CH.sub.2Cl, --CH.sub.2--CHCl.sub.2,
--CH.sub.2--CCl.sub.3, --CH.sub.2--CH.sub.2Br
--CH.sub.2--CHBr.sub.2, --CH.sub.2--CBr.sub.3,
--CH.sub.2--CH.sub.21, --CH.sub.2--CH.sub.12, --CH.sub.2--Cl.sub.3,
--CH.sub.3, --C.sub.2H.sub.5, --C.sub.3H.sub.7,
-cyclo-C.sub.3H.sub.5, --CH(CH.sub.3).sub.2, --C(CH.sub.3).sub.3,
--C.sub.4H.sub.9, --CH.sub.2--CH(CH.sub.3).sub.2,
--CH(CH.sub.3)--C.sub.2H.sub.5, --C(CH.sub.3).sub.3, -Ph,
--CH.sub.2-Ph, --CPh.sub.3, --CH.dbd.CH.sub.2,
--CH.sub.2--CH.dbd.CH.sub.2, --C(CH.sub.3).dbd.CH.sub.2,
--CH.dbd.CH--CH.sub.3, --C.sub.2H.sub.4--CH.dbd.CH.sub.2,
--CH.dbd.C(CH.sub.3).sub.2, --C.ident.CH, --C.ident.C--CH.sub.3,
--CH.sub.2--C.dbd.CH, --Si(CH.sub.3).sub.3, linear or branched,
substituted or unsubstituted heterocyclyl, linear or branched,
substituted or unsubstituted C.sub.1-C.sub.10-cycloalkyl or two
vicinal residues of R.sup.26-- R.sup.38 form together a linear or
branched, substituted or unsubstituted heterocyclyl or linear or
branched, substituted or unsubstituted C.sub.1-C.sub.10-cycloalkyl
ring;
##STR00007##
and stereoisomeric forms, prodrugs, solvates, hydrates and/or
pharmaceutically acceptable salts thereof.
[0006] As used herein, the term "linear or branched
C.sub.1-C.sub.6-alkyl" refers to --CH.sub.3, --C.sub.2H.sub.5,
--C.sub.3H.sub.7, --CH(CH.sub.3).sub.2, --C.sub.4H.sub.9,
--CH.sub.2--CH(CH.sub.3).sub.2, --CH(CH.sub.3)--C.sub.2H.sub.5,
--C(CH.sub.3).sub.3, --CH(CH.sub.3)--C.sub.3H.sub.7,
--CH.sub.2--CH(CH.sub.3)--C.sub.2H.sub.5,
--CH(CH.sub.3)--CH(CH.sub.3).sub.2, --C.sub.5H.sub.11,
--C(CH.sub.3).sub.2--C.sub.2H.sub.5, --CH.sub.2--C(CH.sub.3).sub.3,
--CH(C.sub.2H.sub.5).sub.2, --C.sub.2H.sub.4--CH(CH.sub.3).sub.2,
--C.sub.6H.sub.13, --C.sub.3H.sub.6--CH(CH.sub.3).sub.2,
--C.sub.2H.sub.4--CH(CH.sub.3)--C.sub.2H.sub.5,
--CH(CH.sub.3)--C.sub.4H.sub.9,
--CH.sub.2--CH(CH.sub.3)--C.sub.3H.sub.7,
--CH(CH.sub.3)--CH.sub.2--CH(CH.sub.3).sub.2,
--CH(CH.sub.3)--CH(CH.sub.3)--C.sub.2H.sub.5,
--CH.sub.2--CH(CH.sub.3)--CH(CH.sub.3).sub.2,
--CH.sub.2--C(CH.sub.3).sub.2--C.sub.2H.sub.5,
--C(CH.sub.3).sub.2--C.sub.3H.sub.7,
--C(CH.sub.3).sub.2--CH(CH.sub.3).sub.2,
--C.sub.2H.sub.4--C(CH.sub.3).sub.3, and
--CH(CH.sub.3)--C(CH.sub.3).sub.3.
[0007] Preferred are --CH.sub.3, --C.sub.2H.sub.5,
--C.sub.3H.sub.7, --CH(CH.sub.3).sub.2, --C.sub.4H.sub.9,
--CH.sub.2--CH(CH.sub.3).sub.2, --CH(CH.sub.3)--C.sub.2H.sub.5,
--C(CH.sub.3).sub.3, and --C.sub.5H.sub.11. Especially preferred
are --CH.sub.3, --C.sub.2H.sub.5, --C.sub.3H.sub.7.
[0008] The term "linear or branched C.sub.1-C.sub.20-alkyl"
preferably refers to "linear or branched C.sub.1-C.sub.6-alkyl" and
--C.sub.7H.sub.15, --C.sub.8H.sub.17, --C.sub.9H.sub.19,
--C.sub.10H.sub.21, --C.sub.11H.sub.23, --C.sub.12H.sub.25,
--C.sub.13H.sub.27, --C.sub.14H.sub.29, --C.sub.15H.sub.31,
--C.sub.16H.sub.33, --C.sub.17H.sub.35, --C.sub.18H.sub.37,
--C.sub.19H.sub.39, --C.sub.20H.sub.41.
[0009] As used herein, the term "C.sub.1-C.sub.10-cycloalkyl"
refers to
##STR00008##
[0010] Preferred are the following cycloalkyls:
##STR00009##
[0011] As used herein, the term "linear or branched
C.sub.2-C.sub.6-alkenyl" refers to --CH.dbd.CH.sub.2,
--CH.sub.2--CH.dbd.CH.sub.2, --CH.dbd.CH--CH.sub.3,
--C.sub.2H.sub.4--CH.dbd.CH.sub.2, --CH.dbd.CH--C.sub.2H.sub.5,
--CH.sub.2--C(CH.sub.3).dbd.CH.sub.2, --CH(CH.sub.3)--CH.dbd.CH,
--CH.dbd.C(CH.sub.3).sub.2, --C(CH.sub.3).dbd.CH--CH.sub.3,
--CH.dbd.CH--CH.dbd.CH.sub.2, --C.sub.3H.sub.6--CH.dbd.CH.sub.2,
--C.sub.2H.sub.4--CH.dbd.CH--CH.sub.3,
--CH.sub.2--CH.dbd.CH--C.sub.2H.sub.5, --CH.dbd.CH--C.sub.3H.sub.7,
--CH.sub.2--CH.dbd.CH--CH.dbd.CH.sub.2,
--CH.dbd.CH--CH.dbd.CH--CH.sub.3,
--CH.dbd.CH--CH.sub.2--CH.dbd.CH.sub.2,
--C(CH.sub.3).dbd.CH--CH.dbd.CH.sub.2,
--CH.dbd.C(CH.sub.3)--CH.dbd.CH.sub.2,
--CH.dbd.CH--C(CH.sub.3).dbd.CH.sub.2,
--C.sub.2H.sub.4--C(CH.sub.3).dbd.CH.sub.2,
--CH.sub.2--CH(CH.sub.3)--CH.dbd.CH.sub.2,
--CH(CH.sub.3)--CH.sub.2--CH.dbd.CH.sub.2,
--CH.sub.2--CH.dbd.C(CH.sub.3).sub.2,
--CH.sub.2--C(CH.sub.3).dbd.CH--CH.sub.3,
--CH(CH.sub.3)--CH.dbd.CH--CH.sub.3,
--CH.dbd.CH--CH(CH.sub.3).sub.2,
--CH.dbd.C(CH.sub.3)--C.sub.2H.sub.5,
--C(CH.sub.3).dbd.CH--C.sub.2H.sub.5,
--C(CH.sub.3).dbd.C(CH.sub.3).sub.2,
--C(CH.sub.3).sub.2--CH.dbd.CH.sub.2,
--CH(CH.sub.3)--C(CH.sub.3).dbd.CH.sub.2,
--C(CH.sub.3).dbd.CH--CH.dbd.CH.sub.2,
--CH.dbd.C(CH.sub.3)--CH.dbd.CH.sub.2,
--CH.dbd.CH--C(CH.sub.3).dbd.CH.sub.2,
--C.sub.4H.sub.8--CH.dbd.CH.sub.2,
--C.sub.3H.sub.6--CH.dbd.CH--CH.sub.3,
--C.sub.2H.sub.4--CH.dbd.CH--C.sub.2H.sub.5,
--CH.sub.2--CH.dbd.CH--C.sub.3H.sub.7, --CH.dbd.CH--C.sub.4H.sub.9,
--C.sub.3H.sub.6--C(CH.sub.3).dbd.CH.sub.2,
--C.sub.2H.sub.4--CH(CH.sub.3)--CH.dbd.CH.sub.2,
--CH.sub.2--CH(CH.sub.3)--CH.sub.2--CH.dbd.CH.sub.2,
--CH.sub.2--CH.dbd.CH--CH.sub.3,
--CH(CH.sub.3)--C.sub.2H.sub.4--CH.dbd.CH.sub.2,
--C.sub.2H.sub.4--CH.dbd.C(CH.sub.3).sub.2,
--C.sub.2H.sub.4--C(CH.sub.3).dbd.CH--CH.sub.3,
--CH.sub.2--CH(CH.sub.3)--CH.dbd.CH--CH.sub.3,
--CH(CH.sub.3)--CH.sub.2--CH.dbd.CH--CH.sub.3,
--C(CH.sub.3).dbd.CH.sub.2,
--CH.sub.2--CH.dbd.CH--CH(CH.sub.3).sub.2,
--CH.sub.2--CH.dbd.C(CH.sub.3)--C.sub.2H.sub.5,
--CH.sub.2--C(CH.sub.3).dbd.CH--C.sub.2H.sub.5,
--CH(CH.sub.3)--CH.dbd.CH--C.sub.2H.sub.5,
--CH.dbd.CH--CH.sub.2--CH(CH.sub.3).sub.2,
--CH.dbd.CH--CH(CH.sub.3)--C.sub.2H.sub.5,
--CH.dbd.C(CH.sub.3)--C.sub.3H.sub.7,
--C(CH.sub.3).dbd.CH--C.sub.3H.sub.7,
--CH.sub.2--CH(CH.sub.3)--C(CH.sub.3).dbd.CH.sub.2,
--CH(CH.sub.3)--CH.sub.2--C(CH.sub.3).dbd.CH.sub.2,
--CH(CH.sub.3)--CH(CH.sub.3)--CH.dbd.CH.sub.2,
--CH.sub.2--C(CH.sub.3).sub.2--CH.dbd.CH.sub.2,
--C(CH.sub.3).sub.2--CH.sub.2--CH.dbd.CH.sub.2,
--CH.sub.2--C(CH.sub.3).dbd.C(CH.sub.3).sub.2,
--CH(CH.sub.3)--CH.dbd.C(CH.sub.3).sub.2,
--C(CH.sub.3).sub.2--CH.dbd.CH--CH.sub.3,
--CH(CH.sub.3)--C(CH.sub.3).dbd.CH--CH.sub.3,
--CH.dbd.C(CH.sub.3)--CH(CH.sub.3).sub.2,
--C(CH.sub.3).dbd.CH--CH(CH.sub.3).sub.2,
--C(CH.sub.3).dbd.C(CH.sub.3)--C.sub.2H.sub.5,
--C(CH.sub.3).sub.2--C(CH.sub.3).dbd.CH.sub.2,
--CH(C.sub.2H.sub.5)--C(CH.sub.3).dbd.CH.sub.2,
--C(CH.sub.3)(C.sub.2H.sub.5)--CH.dbd.CH.sub.2,
--CH(CH.sub.3)--C(C.sub.2H.sub.5).dbd.CH.sub.2,
--CH.sub.2--C(C.sub.2H.sub.5).dbd.CH--CH.sub.3,
--C[CH.sub.2--CH(CH.sub.3).sub.2].dbd.CH.sub.2,
--C.sub.2H.sub.4--CH.dbd.CH--CH.dbd.CH.sub.2,
--CH.sub.2--CH.dbd.CH--CH.sub.2--CH.dbd.CH.sub.2,
--CH.dbd.CH--C.sub.2H.sub.4--CH.dbd.CH.sub.2,
--CH.dbd.CH--C(CH.sub.3).sub.3,
--CH.sub.2--CH.dbd.CH--CH.dbd.CH--CH.sub.3,
--CH.dbd.CH--CH.sub.2--CH.dbd.CH--CH.sub.3,
--C[CH(CH.sub.3)(C.sub.2H.sub.5)].dbd.CH.sub.2,
--CH.dbd.CH--CH.dbd.CH--C.sub.2H.sub.5,
--CH.sub.2--CH.dbd.CH--C(CH.sub.3).dbd.CH.sub.2,
--C(C.sub.2H.sub.5).dbd.CH--C.sub.2H.sub.5,
--CH.sub.2--CH.dbd.C(CH.sub.3)--CH.dbd.CH.sub.2,
--CH.sub.2--C(CH.sub.3).dbd.CH--CH.dbd.CH.sub.2,
--C(C.sub.2H.sub.5).dbd.C(CH.sub.3).sub.2,
--CH(CH.sub.3)--CH.dbd.CH--CH.dbd.CH.sub.2,
--CH.dbd.CH--CH.sub.2--C(CH.sub.3).dbd.CH.sub.2,
--C(C.sub.4H.sub.9).dbd.CH.sub.2,
--CH.dbd.CH--CH(CH.sub.3)--CH.dbd.CH.sub.2,
--CH.dbd.C(CH.sub.3)--CH.sub.2--CH.dbd.CH.sub.2,
--C[C(CH.sub.3).sub.3].dbd.CH.sub.2,
--CH.dbd.C(CH.sub.3)--CH.dbd.CH--CH.sub.3,
--C(CH.sub.3).dbd.CH--CH.sub.2--CH.dbd.CH.sub.2,
--CH(C.sub.2H.sub.5)--CH.dbd.CH--CH.sub.3,
--CH.dbd.CH--C(CH.sub.3).dbd.CH--CH.sub.3,
--CH.dbd.CH--CH.dbd.C(CH.sub.3).sub.2,
--C(C.sub.3H.sub.7).dbd.CH--CH.sub.3,
--C(CH.sub.3).dbd.CH--CH.dbd.CH--CH.sub.3,
--CH.dbd.C(CH.sub.3)--C(CH.sub.3).dbd.CH.sub.2,
--CH.sub.2--C(C.sub.3H.sub.7).dbd.CH.sub.2,
--C(CH.sub.3).dbd.CH--C(CH.sub.3).dbd.CH.sub.2,
--C(CH.sub.3).dbd.C(CH.sub.3)--CH.dbd.CH.sub.2, and
--CH.dbd.CH--CH.dbd.CH--CH.dbd.CH.sub.2.
[0012] Preferred are --CH.dbd.CH.sub.2,
--CH.sub.2--CH.dbd.CH.sub.2, --C(CH.sub.3).dbd.CH.sub.2,
--CH.dbd.CH--CH.sub.3, --C.sub.2H.sub.4--CH.dbd.CH.sub.2,
--CH.sub.2--CH.dbd.CH--CH.sub.3. Especially preferred are
--CH.dbd.CH.sub.2--CH.sub.2--CH.dbd.CH.sub.2.
[0013] As used herein, the term "linear or branched
C.sub.2-C.sub.6-alkynyl" refers to --C.ident.CH,
--C.ident.C--CH.sub.3, --CH.sub.2--C.ident.CH,
--C.sub.2H.sub.4--C.ident.CH, --CH.sub.2--C.ident.C--CH.sub.3,
--C.ident.C--C.sub.2H.sub.5, --C.sub.3H.sub.6--C.ident.CH,
--C.sub.2H.sub.4--C.ident.C--CH.sub.3,
--CH.sub.2--C.ident.C--C.sub.2H.sub.5, --C.ident.C--C.sub.3H.sub.7,
--CH(CH.sub.3)--C.ident.CH, --CH.sub.2--CH(CH.sub.3)--C.ident.CH,
--CH(CH.sub.3)--CH.sub.2--C.ident.CH,
--CH(CH.sub.3)--C.ident.C--CH.sub.3, --C.sub.4H.sub.8--C.ident.CH,
--C.sub.3H.sub.6--C.ident.C--CH.sub.3,
--C.sub.2H.sub.4--C.ident.C--C.sub.2H.sub.5,
--CH.sub.2--C.ident.C--C.sub.3H.sub.7,
--C.sub.2H.sub.4--CH(CH.sub.3)--C.ident.CH,
--CH.sub.2--CH(CH.sub.3)--CH.sub.2--C.ident.CH,
--CH(CH.sub.3)--C.sub.2H.sub.4--C.ident.CH,
--CH.sub.2--CH(CH.sub.3)--C.ident.C--CH.sub.3,
--CH(CH.sub.3)--CH.sub.2--C.ident.C--CH.sub.3,
--CH(CH.sub.3)--C.ident.C--C.sub.2H.sub.5,
--CH.sub.2--C.ident.C--CH(CH.sub.3).sub.2,
--C.ident.C--CH(CH.sub.3)--C.sub.2H.sub.5,
--C.ident.C--CH.sub.2--CH(CH.sub.3).sub.2,
--C.ident.C--C.sub.4H.sub.9, --C.ident.C--C(CH.sub.3).sub.3,
--CH(C.sub.2H.sub.5)--C.ident.C--CH.sub.3,
--C(CH.sub.3).sub.2--C.ident.C--CH.sub.3,
--CH(C.sub.2H.sub.5)--CH.sub.2--C.ident.CH,
--CH.sub.2--CH(C.sub.2H.sub.5)--C.ident.CH,
--C(CH.sub.3).sub.2--CH.sub.2--C.ident.CH,
--CH.sub.2--C(CH.sub.3).sub.2--C.ident.CH,
--CH(CH.sub.3)--CH(CH.sub.3)--C.ident.CH,
--CH(C.sub.3H.sub.7)--C.ident.CH,
--C(CH.sub.3)(C.sub.2H.sub.5)--C.ident.CH, --C.ident.C--C.ident.CH,
--CH.sub.2--C.ident.C--C.ident.CH,
--C.ident.C--C.ident.C--CH.sub.3, --CH(C.ident.CH).sub.2,
--C.sub.2H.sub.4--C.ident.C--C.ident.CH,
--CH.sub.2--C.ident.C--CH.sub.2--C.ident.CH,
--C.ident.C--C.sub.2H.sub.4--C.ident.CH,
--CH.sub.2--C.ident.C--CE-C--CH.sub.3,
--C.ident.C--CH.sub.2--C.ident.C--CH.sub.3,
--C.ident.C--C.ident.C--C.sub.2H.sub.5,
--C.ident.C--CH(CH.sub.3)--C.ident.CH,
--CH(CH.sub.3)--C.ident.C--C.ident.CH,
--CH(C.ident.CH)--CH.sub.2--C.ident.CH,
--C(C.ident.CH).sub.2--CH.sub.3, --CH.sub.2--CH(C.ident.CH).sub.2,
--CH(C.ident.CH)--C.ident.C--CH.sub.3. Preferred are --C.ident.CH
and --C.ident.C--CH.sub.3.
[0014] As used herein, the term "aryl" refers to phenyl, indenyl,
indanyl, naphthyl, 1,2-dihydro-naphthyl, 2,3-dihydronaphthyl,
1,2,3,4-tetrahydronaphthyl (tetralinyl), fluorenyl, anthryl
(anthracenyl), 9,10-dihydroanthryl, 1,2,3,4-tetrahydro-anthryl,
1,2,3,4,5,6,7,8-octahydro-anthryl, azulenyl, diphenylmethyl,
benzyl, triphenylmethyl (trityl), styryl, naphthoquinonyl,
acenaphthyl, anthraquinonyl, phenanthryl (phenanthrenyl) and
especially to a mono- or bicyclic 6 to 10 membered ring system,
preferably phenyl or napthyl.
[0015] As used herein, the term "heteroaryl" refers to
heteroaromatic groups which have from 5 to 10 ring atoms, from 1 to
4 of which are selected from O, N and/or S. Preferred groups have 1
or 2 heteroatoms in a 5- or 6-membered aromatic ring. Mono and
bicyclic ring systems are included. Typical heteroaryl groups which
are at least partially aromatic include pyridyl, furyl, thienyl,
pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl,
isothiazolyl, oxadiazolyl, pyridazinyl, pyrimidyl, pyrazinyl,
1,3,5-triazinyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, indolizinyl,
indolyl, isoindolyl, benzo[b]furyl, thiophenyl, benzo[b]thienyl,
indazolyl, benzimidazolyl, benzthiazolyl, thiazolyl, purinyl,
quinolizinyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl,
1,8-naphthyridinyl, tetrahydroquinolyl, benzooxazolyl,
chrom-2-onyl, indazolyl, indenyl. Said heteroaryl groups may
further be substituted by one, two, three, four, five or more
substituents selected from the group consisting of
R.sup.26-R.sup.38, linear or branched C.sub.1-C.sub.20-alkyl,
C.sub.1-C.sub.10-cycloalkyl, linear or branched
C.sub.2-C.sub.6-alkenyl, linear or branched C.sub.2-C.sub.6-alkynyl
and aryl.
[0016] Preferred heterocyclic group are:
##STR00010## ##STR00011## ##STR00012## ##STR00013##
##STR00014##
[0017] Said preferred heteroaryl groups may further be substituted
by one, two, three, four, five or more substituents selected from
the group consisting of R.sup.26-- R.sup.38 linear or branched
C.sub.1-C.sub.20-alkyl, C.sub.1-C.sub.10-cycloalkyl, linear or
branched C.sub.2-C.sub.6-alkenyl, linear or branched
C.sub.2-C.sub.6-alkynyl and aryl.
[0018] As used herein, the term "heterocyclyl" refers to
carbocycles having at least one heteroatom in the ring such as
oxygen, nitrogen, or sulfur. Such heterocycles may be saturated or
partially unsaturated but not aromatic. Examples for heterocyclic
residues are 1,3-dioxolane, benzo[1,3]dioxolyl, pyrazolinyl,
pyranyl, thiomorpholinyl, pyrazolidinyl, piperidyl, piperazinyl,
1,4-dioxanyl, imidazolinyl, pyrrolinyl, imidazolidinyl,
morpholinyl, 1,4-dithianyl, pyrrolidinyl, oxozolinyl, oxazolidinyl,
isoxazolinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl,
isothiazolinyl, isothiazolidinyl, dihydropyranl, pyrrolidinyl,
tetrahydrothiophenyl, tetrahydrofuranyl.
[0019] The term "substituted" or "substituted alkyl", "substituted
cycloalkyl", "substituted heterocyclyl", "substituted aryl",
"substituted heteroaryl", respectively shall refer to the addressed
residue such as "alkyl", "cycloalkyl", "heterocyclyl", "aryl", or
"heteroaryl" bearing one, two, three, four, five or more,
preferably one or two substituents independently selected from the
following group: --OH, --OCH.sub.3, --OC.sub.2H.sub.5,
--OC.sub.3H.sub.7, --O-cyclo-C.sub.3H.sub.5, --OCH(CH.sub.3).sub.2,
--OC(CH.sub.3).sub.3, --OC.sub.4H.sub.9, --OPh, --OCH.sub.2-Ph,
--OCPh.sub.3, --SH, --SCH.sub.3, --SC.sub.2H.sub.5,
--SC.sub.3H.sub.7, --S-cyclo-C.sub.3H.sub.5, --SCH(CH.sub.3).sub.2,
--SC(CH.sub.3).sub.3, --NO.sub.2, --F, --Cl, --Br, --I, --N.sub.3,
--CN, --OCN, --NCO, --SCN, --NCS, --CHO, --COCH.sub.3,
--COC.sub.2H.sub.5, --COC.sub.3H.sub.7, --CO-cyclo-C.sub.3H.sub.5,
--COCH(CH.sub.3).sub.2, --COC(CH.sub.3).sub.3, --COOH, --COCN,
--COOCH.sub.3, --COOC.sub.2H.sub.5, --COOC.sub.3H.sub.7,
--COO-cyclo-C.sub.3H.sub.5, --COOCH(CH.sub.3).sub.2,
--COOC(CH.sub.3).sub.3, --OOC--CH.sub.3, --OOC--C.sub.2H.sub.5,
--OOC--C.sub.3H.sub.7, --OOC-cyclo-C.sub.3H.sub.5,
--OOC--CH(CH.sub.3).sub.2, --OOC--C(CH.sub.3).sub.3, --CONH.sub.2,
--CONHCH.sub.3, --CONHC.sub.2H.sub.5, --CONHC.sub.3H.sub.7,
--CONH-cyclo-C.sub.3H.sub.5, --CONH[CH(CH.sub.3).sub.2],
--CONH[C(CH.sub.3).sub.3], --CON(CH.sub.3).sub.2,
--CON(C.sub.2H.sub.5).sub.2, --CON(C.sub.3H.sub.7).sub.2,
--CON(cyclo-C.sub.3H.sub.5).sub.2, --CON[CH(CH.sub.3).sub.2].sub.2,
--CON[C(CH.sub.3).sub.3].sub.2, --NH.sub.2, --NHCH.sub.3,
--NHC.sub.2H.sub.5, --NHC.sub.3H.sub.7, --NH-cyclo-C.sub.3H.sub.5,
--NHCH(CH.sub.3).sub.2, --NHC(CH.sub.3).sub.3, --N(CH.sub.3).sub.2,
--N(C.sub.2H.sub.5).sub.2, --N(C.sub.3H.sub.7).sub.2,
--N(cyclo-C.sub.3H.sub.5).sub.2, --N[CH(CH.sub.3).sub.2].sub.2,
--N[C(CH.sub.3).sub.3].sub.2, --SOCH.sub.3, --SOC.sub.2H.sub.5,
--SOC.sub.3H.sub.7, --SO-cyclo-C.sub.3H.sub.5,
--SOCH(CH.sub.3).sub.2, --SOC(CH.sub.3).sub.3, --SO.sub.2CH.sub.3,
--SO.sub.2C.sub.2H.sub.5, --SO.sub.2C.sub.3H.sub.7,
--SO.sub.2-cyclo-C.sub.3H.sub.5, --SO.sub.2CH(CH.sub.3).sub.2,
--SO.sub.2C(CH.sub.3).sub.3, --SO.sub.3H, --SO.sub.3CH.sub.3,
--SO.sub.3C.sub.2H.sub.5, --SO.sub.3C.sub.3H.sub.7,
--SO.sub.3-cyclo-C.sub.3H.sub.5, --SO.sub.3CH(CH.sub.3).sub.2,
--SO.sub.3C(CH.sub.3).sub.3, --OCF.sub.3, --OC.sub.2F.sub.5,
--O--COOCH.sub.3, --O--COOC.sub.2H.sub.5, --O--COOC.sub.3H.sub.7,
--O--COO-cyclo-C.sub.3H.sub.5, --O--COOCH(CH.sub.3).sub.2,
--O--COOC(CH.sub.3).sub.3, --NH--CO--NH.sub.2,
--NH--CO--NHCH.sub.3, --NH--CO--NHC.sub.2H.sub.5,
--NH--CO--NHC.sub.3H.sub.7, --NH--CO--NH-cyclo-C.sub.3H.sub.5,
--O--CO--NH.sub.2, --O--CO--NHCH.sub.3, --O--CO--NHC.sub.2H.sub.5,
--O--CO--NHC.sub.3H.sub.7, --O--CO--NH-cyclo-C.sub.3H.sub.5,
--O--CO--NH[CH(CH.sub.3).sub.2], --O--CO--NH[C(CH.sub.3).sub.3],
--O--CO--N(CH.sub.3).sub.2, --O--CO--N(C.sub.2H.sub.5).sub.2,
--O--CO--N(C.sub.3H.sub.7).sub.2,
--O--CO--N(cyclo-C.sub.3H.sub.5).sub.2,
--O--CO--N[CH(CH.sub.3).sub.2].sub.2,
--O--CO--N[C(CH.sub.3).sub.3].sub.2, --O--CO--OCH.sub.3,
--O--CO--OC.sub.2H.sub.5, --O--CO--OC.sub.3H.sub.7,
--O--CO--O-cyclo-C.sub.3H.sub.5, --O--CO--OCH(CH.sub.3).sub.2,
--O--CO--OC(CH.sub.3).sub.3, --CH.sub.2F--CHF.sub.2, --CF.sub.3,
--CH.sub.2Cl, --CHCl.sub.2, --CCl.sub.3, --CH.sub.2Br --CHBr.sub.2,
--CBr.sub.3, --CH.sub.21--CH.sub.12, --Cl.sub.3,
--CH.sub.2--CH.sub.2F--CH.sub.2--CHF.sub.2, --CH.sub.2--CF.sub.3,
--CH.sub.2--CH.sub.2Cl, --CH.sub.2--CHCl.sub.2,
--CH.sub.2--CCl.sub.3, --CH.sub.2--CH.sub.2Br
--CH.sub.2--CHBr.sub.2, --CH.sub.2--CBr.sub.3,
--CH.sub.2--CH.sub.21, --CH.sub.2--CH.sub.12, --CH.sub.2--Cl.sub.3,
-cyclo-C.sub.3H.sub.5, -Ph, --CH.sub.2-Ph, --CPh.sub.3,
--CH.dbd.CH.sub.2, --CH.sub.2--CH.dbd.CH.sub.2,
--C(CH.sub.3).dbd.CH.sub.2, --CH.dbd.CH--CH.sub.3,
--C.sub.2H.sub.4--CH.dbd.CH.sub.2, --CH.dbd.C(CH.sub.3).sub.2,
--C.ident.CH, --C.ident.C--CH.sub.3, --CH.sub.2--C.dbd.CH,
--CH.sub.3, --C.sub.2H.sub.5, --C.sub.3H.sub.7,
--CH(CH.sub.3).sub.2, --C.sub.4H.sub.9,
--CH.sub.2--CH(CH.sub.3).sub.2, --CH(CH.sub.3)--C.sub.2H.sub.5,
--C(CH.sub.3).sub.3, --CH(CH.sub.3)--C.sub.3H.sub.7,
--CH.sub.2--CH(CH.sub.3)--C.sub.2H.sub.5,
--CH(CH.sub.3)--CH(CH.sub.3).sub.2, --C.sub.5H.sub.11,
--C(CH.sub.3).sub.2--C.sub.2H.sub.5, --CH.sub.2--C(CH.sub.3).sub.3,
--CH(C.sub.2H.sub.5).sub.2, --C.sub.2H.sub.4--CH(CH.sub.3).sub.2,
--C.sub.6H.sub.13, --C.sub.3H.sub.6--CH(CH.sub.3).sub.2,
--C.sub.2H.sub.4--CH(CH.sub.3)--C.sub.2H.sub.5,
--CH(CH.sub.3)--C.sub.4H.sub.9,
--CH.sub.2--CH(CH.sub.3)--C.sub.3H.sub.7,
--CH(CH.sub.3)--CH.sub.2--CH(CH.sub.3).sub.2,
--CH(CH.sub.3)--CH(CH.sub.3)--C.sub.2H.sub.5,
--CH.sub.2--CH(CH.sub.3)--CH(CH.sub.3).sub.2,
--CH.sub.2--C(CH.sub.3).sub.2--C.sub.2H.sub.5,
--C(CH.sub.3).sub.2--C.sub.3H.sub.7,
--C(CH.sub.3).sub.2--CH(CH.sub.3).sub.2,
--C.sub.2H.sub.4--C(CH.sub.3).sub.3, and
--CH(CH.sub.3)--C(CH.sub.3).sub.3.
[0020] The term "--CO--O-(linear or branched, substituted or
unsubstituted C.sub.1-C.sub.6-alkyl)" refers to the residue "linear
or branched, substituted or unsubstituted C.sub.1-C.sub.6-alkyl"
connected to the group "--CO--O--" through the oxygen atom.
Accordingly, the term "--CH.sub.2--CO--O-(linear or branched,
substituted or unsubstituted C.sub.1-C.sub.6-alkyl)" refers to the
residue "linear or branched, substituted or unsubstituted
C.sub.1-C.sub.6-alkyl" connected to the group "--CH.sub.2--CO--O--"
through the oxygen atom.
[0021] The following subformula (IIA)-(IIW) of formula (I) are
especially preferred:
##STR00015## ##STR00016## ##STR00017##
wherein R.sup.1-R.sup.39, X and Z have the meanings as defined
above.
[0022] Furthermore, the following subformula (IIIA)-(IIIG) of
formula (I) are also especially preferred:
##STR00018##
wherein R.sup.1-R.sup.39, X and Z have the meanings as defined
above.
[0023] Also especially preferred are the compounds of the following
general formula (IA)-(IF):
##STR00019##
wherein R.sup.1-R.sup.39, X and Z have the meanings as defined
above.
[0024] In yet another preferred embodiment of the present invention
the compound according to the general formula (I) is selected from
the group of compounds depicted in Table 1.
TABLE-US-00001 TABLE I Claimed compounds according to the present
invention LC ret. time MS No. MW IUPAC name [min] [M + H]+ 1 318.14
(3E,4aS,5S)-3-(3,4-Difluorbenzyliden)-4,4a,5,6,7,8- 2.33 318.15
hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one 2 298.16
(3E,4aS,5S)-3-(4-Hydroxybenzyliden)-4,4a,5,6,7,8- 3.05 298.17
hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one 3 334.11
(3E,4aS,5S)-3-(2-Chlor-6-fluorbenzyliden)-4,4a,5,6,7,8- 2.40 334.13
hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one 4 322.16
(3E,4aS,5S)-3-[(Benzofuran-2-yl)methylen]-4,4a,5,6,7,8- 3.09 322.15
hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one 5 342.18
(3E,4aS,5S)-3-(3,4-Dimethoxybenzyliden)-4,4a,5,6,7,8- 2.94 342.19
hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one 6 372.19
(3E,4aS,5S)-3-(3,4,5-Trimethoxybenzyliden)-4,4a,5,6,7,8- 3.01
372.20 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 7
316.12 (3E,4aS,5S)-3-(4-Chlorobenzyliden)-4,4a,5,6,7,8-hexahydro-
2.18 316.10 5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 8 272.14
(3E,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro- 2.87
272.13 5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 9 366.03
(3E,4aS,5S)-3-[(4-Bromthiophen-2-yl)methylen]-4,4a,5,6,7,8- 3.14
366.03 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 10
283.16 (3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.78
284.16 dimethyl-3-[(pyridin-3-yl)methylen]naphthalen-2(3H)-one 11
328.15 (3E,4aS,5S)-3-[4-(Methylthio)benzyliden]-4,4a,5,6,7,8- 2.69
328.16 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 12
322.08 (3E,4aS,5S)-3-[(4-Chlorthiophen-2-yl)methylen]-4,4a,5,6,7,8-
3.03 322.06 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
13 285.17
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl- 2.81
285.15 3-[(1-methyl-1H-pyrrol-2-yl)methylen]naphthalen-2(3H)-on 14
328.17 (3E,4aS,5S)-3-(2-Hydroxy-4-methoxybenzyliden)-4,4a,5,6, 3.24
328.18 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 15
340.20 (3E,4aS,5S)-3-(2-Ethyl-4-methoxybenzyliden)-4,4a,5,6,7,8-
2.64 340.21 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
16 326.19
(3E,4aS,5S)-3-(4-Methoxy-2-methylbenzyliden)-4,4a,5,6,7,8- 2.60
326.22 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 17
327.15 (3E,4aS,5S)-3-(4-Nitrobenzyliden)-4,4a,5,6,7,8-hexahydro-5-
2.75 327.13 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 18 282.16
(3E,4aS,5S)-3-Benzyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy- 2.01
286.16 1,4a-dimethyl-naphthalen-2(3H)-one 19 302.13
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl- 2.68
302.13 3-[(4-methylthiophen-2-yl)methylen]naphthalen-2(3H)-one 20
408.30 (3E,4aS,5S)-3-(2-Methyl-4-octyl-benzyliden)-4,4a,5,6,7,8-
2.31 408.32 hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one
21 296.18
(3E,4aS,5S)-3-(3-Methylbenzyliden)-4,4a,5,6,7,8-hexahydro- 2.17
296.17 5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 22 360.30
(3E,4aS,5S)-3-Dodecyliden-4,4a,5,6,7,8-hexahydro-5- 2.34 360.32
hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 23 324.21
(3E,4aS,5S)-3-(4-Ethyl-2-methylbenzyliden)-4,4a,5,6,7,8- 2.40
324.19 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 24
312.17 (3E,4aS,5S)-3-(4-Methoxybenzyliden)-4,4a,5,6,7,8- 2.74
312.18 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-on 25
272.14 (2E,8aS)-2-[(Furan-2-yl)methylen]-3,4,6,7,8,8a-hexahydro-6-
2.84 272.13 hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 26 340.17
3-{(1E)-[(4S,4aS)-1,2,3,4,4a,5-Hexahydro-4-hydroxy-4a,8- 3.14
340.17 dimethyl-7-oxonaphthalen-6(7H)-yliden]methyl}phenylacetat 27
366.03 (3E,4aS,5S)-3-[(5-Bromthiophen-2-yl)methylen]-4,4a,5,6,7,8-
2.89 366.03 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
28 318.14 (3E,4aS,5S)-3-(2,4-Difluorbenzyliden)-4,4a,5,6,7,8- 2.74
318.13 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 29
246.16 (3E,4aS,5S)-3-[(E)-But-2-enyliden]-4,4a,5,6,7,8-hexahydro-5-
2.04 246.18 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 30 288.12
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.51 288.11
dimethyl-3-[(thiophen-2-yl)methylen]naphthalen-2(3H)-one 31 340.17
4-{(1E)-[(4S,4aS)-1,2,3,4,4a,5-Hexahydro-4-hydroxy-4a,8- 2.99
340.17 dimethyl-7-oxonaphthalen-6(7H)-yliden]methyl}phenylacetat 32
248.18 (3E,4aS,5S)-3-Butyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy-
2.10 248.19 1,4a-dimethylnaphthalen-2(3H)-one 33 302.13
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a-dimethyl- 2.81
302.13 3-[(3-methylthiophen-2-yl)methylen]naphthalen-2(3H)-one 34
272.14 (3E,4aS,5S)-3-[(Furan-2-yl)methylen]-4,4a,5,6,7,8-hexahydro-
2.86 272.15 5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 35 283.16
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.70 283.14
dimethyl-3-[(pyridin-4-yl)methylen]naphthalen-2(3H)-one 36 382.19
(3E,4aS,5S)-3-[4-(2-Phenylethinyl)benzyliden]-4,4a,5,6,7,8- 3.07
382.20 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 37
336.17 (3E,4aS,5S)-3-[4-(2-Methoxy-ethinyl)benzyliden]-4,4a,5,6,7,
2.91 336.18 8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
38 406.25
(3E,4aS,5S)-3-[4-(3-tert-Butoxybut-1-inyl)benzyliden]-4,4a,5,6,
2.96 406.28
7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 39 386.22
(3E,4aS,5S)-3-[4-(2-Cyclo-hexenylethinyl)benzyliden]-4,4a,5, 2.71
386.23 6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-on
40 362.22 (3E,4aS,5S)-3-[4-(Hex-1-inyl)benzyliden]-4,4a,5,6,7,8-
2.64 362.23 hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one
41 396.21
(3E,4aS,5S)-3-[4-(2-p-Tolylethinyl)benzyliden]-4,4a,5,6,7,8- 2.78
396.19 hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one 42
400.24 (3E,4aS,5S)-3-[4-(Nona-1,8-diinyl)benzyliden]-4,4a,5,6,7,8-
3.07 400.24 hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one
43 502.38
(3E,4aS,5S)-3-[4-(Hexadec-1-inyl)benzyliden]-4,4a,5,6,7,8- 3.28
502.36 hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-one 44
364.20 (3E,4aS,5S)-3-[4-(3-Hydroxy-3-methylbut-1-inyl)benzyliden]-
3.11 364.22
4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-
2(3H)-one 45 446.31
(3E,4aS,5S)-3-[4-(Dodec-1-inyl)benzyliden]-4,4a,5,6,7,8- 3.04
446.31 hexahydro-5-hydroxy-1,4a-dimethyl-naphthalen-2(3H)-on 46
408.23 (3E,4aS,5S)-3-[4-(3,3-Diethoxyprop-1-inyl)benzyliden]- 2.94
408.24 4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-
2(3H)-on 47 373.20
6-{4-{(1E)-[(43,4aS)-1,2,3,4,4a,5-Hexahydro-4-hydroxy-4a,8- 2.98
373.20 dimethyl-7-oxonaphthalen-6(7H)-yliden]-methyl}phenyl}hex-5-
in-nitril 48 404.23
(3E,4aS,5S)-3-{4-[2-(1-Hydroxycyclohexyl)ethinyl]benzyliden}- 3.12
404.23 4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-
2(3H)-one 49 400.18
(3E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}- 2.79 400.16
4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen- 2(3H)-one
50 439.25 (3E,4aS,5S)-3-{4-[3-(N-Ethyl-N-benzylamino)prop-1-inyl]-
2.98 439.26 benzyliden}-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-
dimethylnaphthalen-2(3H)-one 51 363.22
(3E,4aS,5S)-3-{4-[3-(Dimethylamino)prop-1-inyl]benzyliden}- 2.86
363.22 4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-
2(3H)-one 52 396.21
(3E,4aS,5S)-3-[4-(3-Phenylprop-1-inyl)benzyliden]-4,4a,5,6,7, 2.60
396.20 8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-on 53
378.20 (3E,4aS,5S)-3-{4-[2-(Trimethylsilyl)ethinyl]benzyliden}-
2.92 378.20
4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen- 2(3H)-on
54 590.34
(35,4aS,5S)-3-[4-(17-Ethinyl-ostradiol)benzyliden]-4,4a,5,6,7, 4.22
590.31 8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 55
350.19
(3E,4aS,5S)-3-[4-(4-Hydroxybut-1-inyl)benzyliden]-4,4a,5,6,7, 3.06
350.18 8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 56
346.19
(3E,4aS,5S)-3-[4-(3-Methylbut-3-en-1-inyl)benzyliden]-4,4a,5, 2.71
346.20 6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-on
57 348.21
(3E,4aS,5S)-3-[4-(3-Methylbut-1-inyl)benzyliden]-4,4a,5,6,7,8- 2.66
348.23 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 58
366.20 (3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-3-{2- 4.09
366.21 [(1S,3R,4S,5R)-1,3,4,5-tetrahydroxycyclohexyl]-ethyliden}-
1,4a-dimethylnaphthalen2(3H)-one 59 300.17
(3E,4aS,5S)-3-[3-(Furan-2-yl)propyliden]-4,4a,5,6,7,8- 2.91 300.16
hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 60 298.16
(3E,4aS,5S)-3-[(E)-3-(Furan-2-yl)allyliden]-4,4a,5,6,7,8- 2.94
298.16 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 61
352.24 (3E,4aS,5S)-3-(2,3,4,5,6-Pentamethylbenzyliden)-4,4a,5,6,
2.91 352.23
7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 62 272.14
(3E,4aS,5S)-3[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro- 2.87
272.15 5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 63 360.07
(3E,4aS,5S)-3-(2-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.58
360.06 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 64 360.07
(3E,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.64
360.06 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 65 360.07
(3E,4aS,5S)-3-(4-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.62
360.09 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 66 388.20
(3E,4aS,5S)-3-[4-(Benzyloxy)benzyliden]-4,4a,5,6,7,8- 2.91 388.21
hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 67 408.06
(3E,4aS,5S)-3-(2-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.90
408.05 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 68 408.06
(3E,4aS,5S)-3-(3-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.98
408.08 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 69 408.06
(3E,4aS,5S)-3-(4-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 3.00
408.06 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 70 326.09
(3E,4aS,5S)-3-(3-Brombutyliden)-4,4a,5,6,7,8-hexahydro-5- 2.66
326.08 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 71 346.19
(3E,4aS,5S)-3-[4-(3-Methylbut-3-en-1-inyl)benzyliden]-4,4a,5, 2.78
346.19 6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-on
72 424.24
(3E,4aS,5S)-3-[4-(5-Phenylpent-1-inyl)benzyliden]-4,4a,5,6, 2.95
424.24 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 73
388.23 (3E,4aS,5S)-3-[4-(2-Cyclohexyl-ethinyl)benzyliden]-4,4a,5,6,
2.86 388.23
7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 74 406.25
(E,4aS,5S)-3-{4-[2-(1-Hydroxycyclohexyl)ethinyl]-benzyliden}- 3.02
406.22 octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 75
530.41 (3E,4aS,5S)-3-[4-(Octadec-1-inyl)benzyliden]-4,4a,5,6,7,8-
3.67 530.40 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
76 486.22 (3E,4aS,5S)-3-{4-[2-(9-Hydroxy-9H-fluoren-9-yl)ethinyl]-
3.24 486.25 benzyliden}-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-
dimethylnaphthalen-2(3H)-one 77 397.09
(1S,8aS)-6-(4-Iodphenylamino)-1,2,3,4,6,7,8,8a-octahydro- 3.08
397.07 5,8a-dimethylnaphthalen-1-ol 78 448.20
(3E,4aS,5S)-3-[4-(2-Methoxy-4-nitrophenylamino)benzyliden]- 3.25
448.24 4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-
2(3H)-one 79 499.10
(3E,4aS,5S)-3-[4-(4-Iodphenylamino)benzyliden]-4,4a,5,6,7,8- 3.11
499.11 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 80
272.14 (3E,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro-
2.80 272.15 5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 81 360.07
(3E,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.74
360.08 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 82 262.19
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.21 262.20
dimethyl-3-(2-methylbutyliden)-naphthalen-2(3H)-one 83 318.14
(E,4aS,5S)-3-(4-Chlorbenzyliden)-octahydro-5-hydroxy-1,4a- 2.80
318.14 dimethylnaphthalen-2(1H)-one 84 330.16
(3E,4aS,5S)-3-(3-Fluor-4-methoxybenzyliden)-4,4a,5,6,7,8- 2.93
330.14 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 85
300.15 (3E,4aS,5S)-3-(4-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-
2.71 300.16 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 86 287.19
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-[(1-methyl- 2.78
287.18 1H-pyrrol-2-yl)methylen]naphthalen-2(1H)-one 87 320.16
(E,4aS,5S)-3-(3,4-Difluorbenzyliden)-octahydro-5-hydroxy- 2.86
320.15 1,4a-dimethylnaphthalen-2(1H)-one 88 336.13
(E,4aS,5S)-3-(2-Chlor-6-fluorbenzyliden)-octahydro-5- 2.94 334.15
hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 89 326.22
(E,4aS,5S)-3-(4-Ethyl-2-methylbenzyliden)-octahydro-5- 2.64 326.22
hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 90 432.30
(3E,4aS,5S)-3-[4-(Undec-1-inyl)benzyliden]-4,4a,5,6,7,8- 2.96
432.31 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 91
390.26 (3E,4aS,5S)-3-[4-(Oct-1-inyl)benzyliden]-4,4a,5,6,7,8- 2.84
390.24 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 92
474.35 (3E,4aS,5S)-3-[4-(Tetradec-1-inyl)benzyliden]-4,4a,5,6,7,8-
3.10 474.38 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
93 438.26
(3E,4aS,5S)-3-{4-[2-(4-tert-Butylphenyl)ethinyl]benzyliden}- 3.02
438.28 4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-
2(3H)-one 94 322.22
(3E,4aS,5S)-3-[4-(3,3-Dimethylbut-1-inyl)benzyliden]-4,4a,5,6, 2.67
322.24 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 95
390.22 (3E,4aS,5S)-3-{4-[2-(1-Hydroxycyclopentyl)ethinyl]- 2.84
390.21 benzyliden}-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-
dimethylnaphthalen-2(3H)-one 96 192.15
(1S,8aS)-1,2,3,4,6,7,8,8a-Octahydro-5,8a-dimethyl-6- 2.02 192.16
methylennaphthalen-1-ol 97 280.18
(1S,7E,8aS)-7-Benzyliden-1,2,3,4,6,7,8,8a-octahydro-5,8a- 2.18
280.18 dimethyl-6-methylennaphthalen-1-ol 98 260.21
(1S,7E,8aS)-1,2,3,4,6,7,8,8a-Octahydro-5,8a-dimethyl-6- 2.24 260.20
methylen-7-pentylidennaphthalen-1-ol 99 264.17 (2E)-Ethyl
2-[(4S,4aS)-2,3,4,4a,5,6-hexahydro-4-hydroxy- 2.46 264.19
4a,8-dimethylnaphthalen-7(1H)-yliden]acetat 100 262.23
(1S,6E,8aS)-6-Hexyliden-1,2,3,4,6,7,8,8a-octahydro-5,8a- 2.21
262.24 dimethylnaphthalen-1-ol 101 268.18
(1S,6E,8aS)-6-Benzyliden-1,2,3,4,6,7,8,8a-octahydro-5,8a- 2.19
268.20 dimethylnaphthalen-1-ol 102 344.24
(1S,8aS)-5-(3,5-Dimethoxybenzyl)-decahydro-5,8a-dimethyl- 2.56
344.23 6-methylennaphthalen-1-ol 103 330.18
(E,4aS,5S)-3-(4-Hydroxy-3-methoxybenzyliden)-octahydro-5- 3.07
330.18 hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 104 336.17
(3E,4aS,5S)-3-[4-(3-Hydroxyprop-1-inyl)benzyliden]-4,4a,5,6, 2.88
336.16 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
105 416.15 (3E,4aS,5S)-3-{4-[2-(4-Chlorphenyl)ethinyl]benzyliden}-
3.05 416.12
4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen- 2(3H)-one
106 396.21
(3E,4aS,5S)-3-[4-(3-Phenylprop-1-inyl)benzyliden]-4,4a,5,6, 2.78
396.20 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
107 330.15 (3E,4aS,5S)-3-(2,3,4-Trihydroxybenzyliden)-4,4a,5,6,7,8-
3.49 330.15 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
108 332.16 (E,4aS,5S)-3-(2,3,4-Trihydroxybenzyliden)-octahydro-5-
3.46 332.16 hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 109 316.13
(3E,4aS,5S)-3-(2,3,4-Trihydroxybenzyliden)-4,4a,5,6,7,8- 3.46
316.12 hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 110 406.18
(3E,4aS,5S)-3-(2,3,4-Trihydroxybenzyliden)-4a-benzyl-4,4a,5, 3.58
406.16 6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 111
264.17 (3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-3-[(R)-3- 2.89
264.16 hydroxybutyliden]-1,4a-dimethylnaphthalen-2(3H)-one 112
266.19 (E,4aS,5S)-Octahydro-5-hydroxy-3-[(R)-3-hydroxybutyliden]-
2.92 266.19 1,4a-dimethylnaphthalen-2(1H)-one 113 250.16
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-3-[(R)-3- 2.90 250.16
hydroxybutyliden]4a-methylnaphthalen-2(3H)-one 114 340.20
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-3- 2.98
340.20 [(R)-3-hydroxybutyliden]-1-methylnaphthalen-2(3H)-one 115
321.17 (3E,4aS,5S)-3-[(1H-Indol-3-yl)methylen]-4,4a,5,6,7,8- 3.01
321.17 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 116
323.19 (E,4aS,5S)-3-[(1H-Indol-3-yl)methylen]-octahydro-5-hydroxy-
2.99 323.22 1,4a-dimethylnaphthalen-2(1H)-one 117 307.16
(3E,4aS,5S)-3-[(1H-Indol-3-yl)methylen]-4,4a,5,6,7,8- 3.01 307.18
hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 118 397.20
(3E,4aS,5S)-3-[(1H-Indol-3-yl)methylen]-4a-benzyl-4,4a,5, 3.10
397.22 6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 119
323.19 (E,5S,8aS)-2-[1H-Indol-3-yl)methylen]-octahydro-6-hydroxy-
2.97 323.19 5,8a-dimethylnaphthalen-1(2H)-one 120 246.16
(3E,4aS,5S)-3-[(E)-But-2-enyliden]-4,4a,5,6,7,8-hexahydro-5- 2.52
246.15 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 121 248.18
(3E,4aS,5S)-3-[(E)-But-2-enyliden]-octahydro-5-hydroxy-1,4a- 2.49
248.17 dimethylnaphthalen-2(1H)-one 122 232.15
(3E,4aS,5S)-3-[(E)-But-2-enyliden]-4,4a,5,6,7,8-hexahydro-5- 2.54
232.14 hydroxy-4a-methylnaphthalen-2(3H)-one 123 322.19
(3E,4aS,5S)-4a-Benzyl-3-[(E)-but-2-enyliden]-4,4a,5,6,7,8- 2.56
322.17 hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 124 248.18
(2E,8aS)-2-[(E)-But-2-enyliden]-octahydro-6-hydroxy-5,8a- 2.52
248.20 dimethylnaphthalen-1(2H)-one 125 392.27
(E,4aS,5S)-3-[4-(Oct-1-inyl)-benzyliden]-octahydro-5-hydroxy- 2.86
392.27 1,4a-dimethylnaphthalen-2(1H)-one 126 466.29
(3E,4aS,5S)-3-[4-(Oct-1-inyl)benzyliden]-4a-benzyl-4,4a,5,6, 2.89
466.27 7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 127
504.40 (E,4aS,5S)-3-[4-(Hexadec-1-inyl)benzyliden]-octahydro-5-
2.90 504.41 hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 128 578.41
(3E,4aS,5S)-3-[4-(Hexadec-1-inyl)benzyliden]-4a-benzyl-4,4a, 2.94
578.42 5,6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 129
350.22 (E,4aS,5S)-3-[4-(Pent-1-inyl)benzyliden]-octahydro-5- 2.71
350.23 hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 130 424.24
(3E,4aS,5S)-3-[4-(Pent-1-inyl)benzyliden]-4a-benzyl-4,4a,5, 2.76
424.26 6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 131
434.32 (E,4aS,5S)-3-[4-(Undec-1-inyl)benzyliden]-octahydro-5- 3.01
434.30 hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 132 508.33
(3E,4aS,5S)-3-[4-(Undec-1-inyl)benzyliden]-4a-benzyl-4,4a, 3.02
508.30 5,6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 133
476.37 (E,4aS,5S)-3-[4-(Tetradec-1-inyl)benzyliden]-octahydro-5-
3.18 476.39 hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 134 550.38
(3E,4aS,5S)-3-[4-(Tetradec-1-inyl)benzyliden]-4a-benzyl-4,4a, 3.27
550.35 5,6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 135
359.19 (3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-
2.79 359.19 methyl-3-[(pyridin-4-yl)methylen]naphthalen-2(3H)-one
136 368.18
(3E,4aS,5S)-3-[4-(2-Phenylethinyl)benzyliden]-4,4a,5,6,7,8- 2.68
368.17 hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 137 364.19
(3E,4aS,5S)-3-{4-[2-(Trimethylsilyl)ethinyl]benzyliden}-4,4a, 2.56
364.18 5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one
138 390.22
(3E,4aS,5S)-3-{4-[2-(1-Hydroxycyclohexyl)ethinyl]benzyliden}- 2.89
390.21 4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-
2(3H)-one 139 251.22
(1S,8aS)-6-(Butylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a- 2.74
251.22 dimethylnaphthalen-1-ol 140 277.24
(1S,8aS)-6-(Cyclohexylamino)-1,2,3,4,6,7,8,8a-octahydro- 2.69
277.25 5,8a-dimethylnaphthalen-1-ol 141 491.17
(1S,7E,8aS)-7-(4-Iodbenzyliden)-6-(cyclohexylamino)- 3.11 491.17
1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylnaphthalen-1-ol 142 397.09
(1S,8aS)-6-(4-Iodphenylamino)-1,2,3,4,6,7,8,8a-octahydro- 2.78
397.11 5,8a-dimethylnaphthalen-1-ol 143 489.15
(1S,8aS)-6-(4-Iodphenylamino)-5-benzyl-decahydro-5,8a- 2.94 489.16
dimethylnaphthalen-1-ol 144 346.19
(1S,8aS)-6-(2-Methoxy-4-nitrophenylamino)-1,2,3,4,6,7,8,8a- 2.86
346.21 octahydro-5,8a-dimethylnaphthalen-1-ol 145 549.17
(1S,8aS)-5-(3,5-Dimethoxybenzyl)-6-(4-Iodphenylamino)- 3.31 549.14
decahydro-5,8a-dimethylnaphthalen-1-ol 146 429.32
(1S,8aS)-5-(3,5-Dimethoxybenzyl)-6-(cyclohexylamino)- 2.94 429.30
decahydro-5,8a-dimethylnaphthalen-1-ol 147 403.31
(1S,8aS)-5-(3,5-Dimethoxybenzyl)-6-(butylamino)-decahydro- 2.98
403.30 5,8a-dimethylnaphthalen-1-ol 148 465.15
(1S,8aS)-7-(4-Iodbenzyl)-6-(butylamino)-1,2,3,4,6,7,8,8a- 3.04
465.17 octahydro-5,8a-dimethylnaphthalen-1-ol 149 406.25
(4aS,5S)-3-[4-(3-tert-Butoxybut-1-inyl)benzyl]-4,4a,5,6,7,8- 2.93
406.25 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 150
439.25 (4aS,5S)-3-{4-[3-(N-Benzyl-N-methylamino)prop-1- 3.07 439.24
inyl]benzyl}-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-
dimethylnaphthalen-2(3H)-one 151 383.19
(4aS,5S)-{3-[4-(2-(Pyridin-2-yl)ethinyl]benzyl}4,4a,5,6,7,8- 2.92
383.20 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 152
350.19 (4aS,5S)-3-[4-(4-Hydroxybut-1-inyl)benzyl]-4,4a,5,6,7,8-
3.18 250.19 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
153 282.18 Ethyl-2-[(4aS,5S)-decahydro-5-hydroxy-1,4a-dimethyl-2-
2.84 282.18 oxonaphthalen-1-yl]acetat 154 399.22
(3E,4aS,5S)-3-[(9-Ethyl-9H-carbazol-3-yl)methylen]-4,4a,5,6, 3.11
399.20 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
155 452.24
(E,4aS,5S)-1-(3,5-Dimethoxy-benzyl)-3-(4-fluorbenzyliden)- 3.19
452.25 octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 156
494.27 (E,4aS,5S)-3-(3,4-Dimethoxybenzyliden)-1-(3,5-dimethoxy-
3.38 494.29
benzyl)-octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)- one 157
324.17 (E,4aS,5S)-3-[(Benzofuran-2-yl)methylen]-octahydro-5- 2.94
324.16 hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 158 289.20
(3E,4aS,5S)-Octahydro-3-[(4,5-dihydro-3-methyl-1H-pyrrol-2- 2.81
289.20 yl)methylen]-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 159
372.19 (3E,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-4,4a,5,6,7,8-
3.04 372.18 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
160 372.11 (3E,4aS,5R)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.83
372.11 dimethyl-3-(perfluor-benzyliden)naphthalen-2(3H)-one 161
362.09 (E,4aS,5S)-3-(4-Brombenzyliden)-octahydro-5-hydroxy-1,4a-
2.71 362.09 dimethylnaphthalen-2(1H)-one 162 287.19
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-[(1-methyl- 2.64
287.19 1H-pyrrol-2-yl)methylen]naphthalen-2(1H)-one 163 264.21
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-(2-methyl- 2.35
264.20 butyliden)naphthalen-2(1H)-one 164 302.17
(E,4aS,5S)-3-(4-Fluorbenzyliden)-octahydro-5-hydroxy-1,4a- 2.69
302.18 dimethylnaphthalen-2(1H)-one 165 408.06
(3E,4R,4aS,5S)-3-(4-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro- 2.83
408.07 5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 166 316.12
(3E,4R,4aS,5S)-3-(3-Chlorbenzyliden)-4,4a,5,6,7,8- 2.75 316.12
hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 167
5-Hydroxy-1-methyl-7-phenyl-4,4a,5,6,7,8,-hexahydro-3H-
naphthalen-2-one 168 360.07
(3E,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.72
360.07 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 169 360.07
(3E,4aS,5S)-3-(2-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.80
360.08 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 170 220.15
(3E,4aS,5S)-3-Ethyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy- 2.30
220.15 1,4a-dimethylnaphthalen-2(3H)-one 171 374.21
(E,4aS,5S)-3-(2,3,4-Trimethoxy-benzyliden)-octahydro-5- 3.08 374.21
hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 172 330.17
(E,4aS,5S)-3-[4-(Methylthio)-benzyliden]-octahydro-5- 2.88 330.17
hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 173 328.24
(3E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-{[(S)-4- 2.69
328.25 (prop-1-en-2-yl)cyclohex-1-enyl]-methylen}naphthalen-2(1H)-
one 174 288.17 (E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-[(5-
2.74 288.16 methylfuran-2-yl)methylen]naphthalen-2(1H)-one 175
388.20 (3E,4R,4aS,5S)-3-[2-(Benzyloxy)-benzyliden]-4,4a,5,6,7,8-
2.98 388.20 hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one
176 272.14 (3E,4R,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-
2.66 272.15 hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one
177 360.07
(3E,4aS,5S)-3-(4-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.74
360.07 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 178 262.20
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.31 262.20
dimethyl-3-(2-methyl-butylidene)naphthalen-2(3H)-one 179 300.15
(3E,4aS,5S)-3-(4-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.69
300.15 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 180 410.07
(E,4aS,5S)-3-(4-Iodbenzyliden)-octahydro-5-hydroxy-1,4a- 2.83
410.08 dimethylnaphthalen-2(1H)-one 181 264.21
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-(2-methyl- 2.34
264.22 butyliden)naphthalen-2(1H)-one 182 410.07
(E,4aS,5S)-3-(2-Iodbenzyliden)-octahydro-5-hydroxy-1,4a- 2.87
410.08 dimethylnaphthalen-2(1H)-one 183 318.14
(E,4aS,5S)-3-(3-Chlorbenzyliden)-octahydro-5-hydroxy-1,4a- 2.69
318.15 dimethylnaphthalen-2(1H)-one 184 300.15
(3E,4R,4aS,5S)-3-(2-Fluorbenzyliden)-4,4a,5,6,7,8- 2.71 300.16
hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 185 258.13
(3E,4aS,5S)-3-[(Furan-2-yl)methylen]-4,4a,5,6,7,8-hexahydro- 2.74
258.13 5-hydroxy-4a-methylnaphthalen-2(3H)-one 186 372.19
(3E,4aS,5S)-3-(2,3,4-Trimethoxybenzyliden)-4,4a,5,6,7,8- 3.04
372.20 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 187
328.15 (3E,4aS,5S)-3[4-(Methylthio)benzyliden]-4,4a,5,6,7,8- 2.88
328.13 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 188
326.22 (3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.61
326.22
dimethyl-3-{[(S)-4-(prop-1-en-2-yl)cyclohex-1-enyl]methylen}-
naphthalen-2(3H)-one 189 286.16
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.72 286.14
dimethyl-3-[(5-methylfuran-2-yl)methylen]naphthalen-2(3H)-on 190
390.22 (E,4aS,5S)-3-[2-(Benzyloxy)-benzyliden]-octahydro-5- 2.99
390.22 hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 191 408.06
(3E,4R,4aS,5S)-3-(3-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro- 2.85
408.07 5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 192 408.06
(3E,4aS,5S)-3-(4-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.79
408.04 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 193 262.19
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.29 262.18
dimethyl-3-(2-methyl-butyliden)naphthalen-2(3H)-one 194 408.06
(3E,4aS,5S)-3-(2-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.87
408.06 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 195 316.12
(3E,4aS,5S)-3-(3-Chlorbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.74
316.13 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 196 302.17
(E,4aS,5S)-3-(2-Fluorbenzyliden)-octahydro-5-hydroxy-1,4a- 2.80
302.16 dimethylnaphthalen-2(1H)-one 197 372.19
(3E,4R,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-4,4a,5,6,7,8- 3.11
372.19 hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 198
346.06 (3E,4aS,5S)-3-(4-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5-
2.83 346.07 hydroxy-4a-methylnaphthalen-2(3H)-one 199 388.20
(3E,4aS,5S)-3-[2-(Benzyloxy)-benzyliden]-4,4a,5,6,7,8- 3.02 388.20
hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 200 326.22
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.88 326.21
dimethyl-3-[(2,6,6-trimethylcyclohexa-1,3-dienyl)-
methylen]naphthalen-2(3H)-one 201 354.26
(E,4aS,5S)-3-(2,3,4,5,6-Pentamethylbenzyliden)-octahydro-5- 2.81
354.25 hydroxy-1,4a-dimethylnaphthalen-2(1H)-on 202 410.07
(E,4aS,5S)-3-(3-Iodbenzyliden)-octahydro-5-hydroxy-1,4a- 2.81
410.07 dimethylnaphthalen-2(1H)-one 203 282.16
(3E,4R,4aS,5S)-3-Benzyliden-4,4a,5,6,7,8-hexahydro-5- 2.40 282.15
hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 204 360.07
(3E,4R,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8- 2.75 360.09
hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 205 360.07
(3E,4R,4aS,5S)-3-(2-Brombenzyliden)-4,4a,5,6,7,8- 2.79 360.08
hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 206 220.15
(3E,4R,4aS,5S)-3-Ethyliden-4,4a,5,6,7,8-hexahydro-5- 2.29 220.15
hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 207 374.21
(E,4aS,5S)-3-(2,3,4-Trimethoxy-benzyliden)-octahydro-5- 3.08 374.20
hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 208 300.15
(3E,4aS,5S)-3-(2-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.81
300.16 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 209 276.21
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-1,4a- 2.75 276.20
dimethyl-3-(2-methylpentyliden)-naphthalen-2(3H)-one 210 374.21
(E,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-octahydro-5- 3.03 374.19
hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 211 374.13
(E,4aS,5S)-Octahydro-5-hydroxy-1,4a-dimethyl-3-(perfluor- 2.84
374.14 benzyliden)naphthalen-2(1H)-one 212 360.07
(3E,4R,4aS,5S)-3-(4-Brombenzyliden)-4,4a,5,6,7,8- 2.81 360.09
hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 213 300.15
(3E,4R,4aS,5S)-3-(4-Fluorbenzyliden)-4,4a,5,6,7,8- 2.76 300.15
hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 214 394.04
(3E,4aS,5S)-3-(4-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.89
394.05 hydroxy-4a-methylnaphthalen-2(3H)-one 215 352.24
(3E,4aS,5S)-3-(2,3,4,5,6-Pentamethylbenzyliden)-4,4a,5,6, 2.74
352.24 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
216 408.06
(3E,4aS,5S)-3-(3-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.84
408.07 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 217 300.15
(3E,4aS,5S)-3-(3-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.71
300.15 hydroxy-1,4a-dimethylnaphthalen-2(3H)-one 218 362.09
(E,4aS,5S)-3-(3-Brombenzyliden)-octahydro-5-hydroxy-1,4a- 2.79
362.09 dimethylnaphthalen-2(1H)-one 219 362.09
(E,4aS,5S)-3-(2-Brombenzyliden)-octahydro-5-hydroxy-1,4a- 2.83
362.09 dimethylnaphthalen-2(1H)-one 220 222.16
(E,4aS,5S)-3-Ethyliden-octahydro-5-hydroxy-1,4a- 2.34 222.17
dimethylnaphthalen-2(1H)-one 221 372.19
(3E,4R,4aS,5S)-3-(2,3,4-Trimethoxybenzyliden)-4,4a,5,6,7,8- 3.10
372.19 hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one 222
328.15 (3E,4R,4aS,5S)-3-[4-(Methylthio)benzyliden]-4,4a,5,6,7,8-
2.79 328.14 hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H)-one
223 374.19 (3E,4aS,5S)-3-[2-(Benzyloxy)benzyliden]-4,4a,5,6,7,8-
2.98 374.19 hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 224
286.14 (3E,4aS,5S)-3-(2-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5-
2.77 286.14 hydroxy-4a-methylnaphthalen-2(3H)-one 225 262.19
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3- 2.46
262.19 (2-methylpentyliden)naphthalen-2(3H)-one 226 312.14
4-{(1E)-[(4S,4aS)-1,2,3,4,4a,5-Hexahydro-4-hydroxy-4a- 3.24 312.15
methyl-7-oxonaphthalen-6(7H)-yliden]methyl}benzoic acid 227 348.17
(3E,4aS,5S)-4a-Benzyl-3-[(furan-2-yl)methylen]-4,4a,5,6,7,8- 2.94
348.18 hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 228 448.22
(3E,4aS,5S)-3-(2,4,5-Trimethoxy-benzyliden)-4a-benzyl-4,4a, 3.28
448.22 5,6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 229
448.15 (3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-
3.04 448.16 methyl-3-(perfluorbenzyliden)naphthalen-2(3H)-one 230
386.09 (3E,4R,4aS,5S)-3-(4-Brombenzyliden)-4a-allyl-4,4a,5,6,7,8-
3.10 386.09 hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 231
311.19 (3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-
3.00 311.20 methyl-3-[(1-methyl-1H-pyrrol-2-yl)methylen]naphthalen-
2(3H)-one 232 288.21
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4- 2.74
288.21 methyl-3-(2-methylbutylidene)-naphthalen-2(3H)-one 233
396.06 (E,5S)-2-(4-Iodbenzyliden)-octahydro-6-hydroxy-5- 2.86
396.07 methylnaphthalen-1(2H)-one 234 394.04
(3E,4aS,5S)-3-(3-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.79
394.03 hydroxy-4a-methylnaphthalen-2(3H)-one 235 286.14
(3E,4aS,5S)-3-(3-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.66
286.14 hydroxy-4a-methylnaphthalen-2(3H)-one 236 358.18
(3E,4aS,5S)-4a-Benzyl-3-benzyliden-4,4a,5,6,7,8-hexahydro- 2.84
358.18 5-hydroxy-1-methylnaphthalen-2(3H)-one 237 436.10
(3E,4aS,5S)-3-(3-Brombenzyliden)-4a-benzyl-4,4a,5,6,7,8- 3.03
436.10 hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 238 296.18
(3E,4aS,5S)-4a-Benzyl-3-ethyliden-4,4a,5,6,7,8-hexahydro-5- 2.65
286.18 hydroxy-1-methylnaphthalen-2(3H)-one 239 398.21
(3E,4R,4aS,5S)-3-(2,3,4-Trimethoxybenzyliden)-4a-allyl-4, 3.24
398.21 4a,5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)- one
240 354.17
(3E,4R,4aS,5S)-3-[4-(Methylthio)-benzyliden]-4a-allyl-4,4a,5, 3.06
354.16 6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 241
352.24 (3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-
2.98 352.24
methyl-3-{[(S)-4-(prop-1-en-2-yl)cyclohex-1-enyl]methylen}-
naphthalen-2(3H)-one 242 312.17
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4- 3.14
312.18 methyl-3-[(5-methylfuran-2-yl)methylen]naphthalen-2(3H)-on
243 390.22 (E,5S,8aS)-2-(2-(Benzyloxy)-benzyliden)-octahydro-6-
2.86 390.22 hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 244 358.18
(3E,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-4,4a,5,6,7,8- 3.01
358.18 hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 245 358.10
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3- 2.89
358.09 (perfluorbenzyliden)naphthalen-2(3H)-one 246 338.22
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1- 2.69
338.22 methyl-3-(2-methylbutyliden)naphthalen-2(3H)-one 247 376.18
(3E,4aS,5S)-3-(4-Fluorbenzyliden)-4a-benzyl-4,4a,5,6,7,8- 2.87
376.18 hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 248 334.07
(3E,4R,4aS,5S)-3-(4-Iodbenzyliden)-4a-allyl-4,4a,5,6,7,8- 3.02
334.06 hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 249 288.21
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4- 2.68
288.20 methyl-3-(2-methylbutyliden)-naphthalen-2(3H)-one 250 434.07
(3E,4R,4aS,5S)-3-(2-Iodbenzyliden)-4a-allyl-4,4a,5,6,7,8- 3.05
434.06 hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one
251 302.17
(E,5S,8aS)-2-(2-Fluorbenzyliden)-octahydro-6-hydroxy-5,8a- 2.76
302.19 dimethylnaphthalen-1(2H)-one 252 346.06
(3E,4aS,5S)-3-(3-Brombenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.79
346.06 hydroxy-4a-methylnaphthalen-2(3H)-one 253 206.13
(3E,4aS,5S)-3-Ethyliden-4,4a,5,6,7,8-hexahydro-5-hydroxy- 2.24
206.13 4a-methylnaphthalen-2(3H)-one 254 448.22
(3E,4aS,5S)-3-(2,3,4-Trimethoxybenzyliden)-4a-benzyl- 3.31 448.21
4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)- one 255
414.22 (3E,4R,4aS,5S)-3-[2-(Benzyloxy)-benzyliden]-4a-allyl-4,4a,5,
3.15 414.22 6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one
256 352.24
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4- 2.97
352.24 methyl-3-{[(R)-4-(prop-1-en-2-yl)cyclohex-1-enyl]-
methylen}naphthalen-2(3H)-one 257 298.16
(3E,4R,4aS,5S)-4a-Allyl-3-[(furan-3-yl)methylen]-4,4a,5,6,7,8- 3.06
298.18 hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 258 352.24
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4- 2.84
352.24 methyl-3-[(2,6,6-trimethyl-cyclohexa-1,3-dienyl)methylen]-
naphthalen-2(3H)-one 259 354.26
(E,5S,8aS)-2-(2,3,4,5,6-Pentamethyl-benzyliden)-octahydro- 2.76
354.26 6-hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 260 271.16
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3- 2.84
271.16 [(1-methyl-1H-pyrrol-2-yl)methylen]naphthalen-2(3H)-one 261
248.18 (3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-
2.40 248.19 (2-methylbutyliden)naphthalen-2(3H)-one 262 286.14
(3E,4aS,5S)-3-(4-Fluorbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.68
286.12 hydroxy-4a-methylnaphthalen-2(3H)-one 263 338.22
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1- 2.76
338.22 methyl-3-(2-methylbutyliden)naphthalen-2(3H)-one 264 326.17
(3E,4R,4aS,5S)-3-(2-Fluorbenzyliden)-4a-allyl-4,4a,5,6,7,8- 2.88
326.17 hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 265 302.22
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4- 2.75
302.21 methyl-3-(2-methylpentyliden)-naphthalen-2(3H)-one 266
274.16 (E,5S,8aS)-2-[(Furan-2-yl)methylen]-octahydro-6-hydroxy-
2.78 274.17 5,8a-dimethylnaphthalen-1(2H)-one 267 374.21
(E,5S,8aS)-2-(2,4,5-Trimethoxy-benzyliden)-octahydro-6- 2.96 374.22
hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 268 314.13
(3E,4aS,5S)-3-[4-(Methylthio)-benzyliden]-4,4a,5,6,7,8- 2.76 314.14
hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 269 312.21
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3- 2.70
312.19 {[(S)-4-(prop-1-en-2-yl)cyclohex-1-enyl]methylen}naphthalen-
2(3H)-one 270 272.14
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3- 2.73
272.14 [(5-methylfuran-2-yl)methylen]naphthalen-2(3H)-one 271
464.24 (3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3-
3.04 464.24 [(5-methylfuran-2-yl)methylen]naphthalen-2(3H)-one 272
402.26 (3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-
2.94 402.26 methyl-3-{[(S)-4-(prop-1-en-2-yl)cyclohex-1-
enyl]methylen}naphthalen-2(3H)-one 273 378.26
(3E,4R,4aS,5S)-3-(2,3,4,5,6-Pentamethylbenzyliden)-4a-allyl- 2.97
378.27 4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-
one 274 434.07
(3E,4R,4aS,5S)-3-(3-Iodbenzyliden)-4a-allyl-4,4a,5,6,7,8- 3.08
434.08 hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 275 326.17
(3E,4R,4aS,5S)-3-(3-Fluorbenzyliden)-4a-allyl-4,4a,5,6,7,8- 3.01
326.19 hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 276 362.09
(E,5S,8aS)-2-(3-Brombenzyliden)-octahydro-6-hydroxy-5,8a- 2.78
362.09 dimethylnaphthalen-1(2H)-one 277 248.18
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3- 2.24
248.17 (2-methylbutyliden)naphthalen-2(3H)-one 278 394.04
(3E,4aS,5S)-3-(2-Iodbenzyliden)-4,4a,5,6,7,8-hexahydro-5- 2.87
394.04 hydroxy-4a-methylnaphthalen-2(3H)-one 279 376.18
(3E,4aS,5S)-3-(2-Fluorbenzyliden)-4a-benzyl-4,4a,5,6,7,8- 2.95
376.18 hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 280 352.24
(3E,4aS,5S)-4a-Benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1- 2.78
352.23 methyl-3-(2-methylpentyliden)naphthalen-2(3H)-one 281 398.21
(3E,4R,4aS,5S)-3-(2,4,5-Trimethoxybenzyliden)-4a-allyl-4,4a, 3.22
334.13 5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 282
260.18 (3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-
2.67 260.18 methyl-3-propylidennaphthalen-2(3H)-one 283 398.13
(3E,4R,4aS,5S)-4a-Allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4- 2.89
398.12 methyl-3-(perfluorbenzyliden)-naphthalen-2(3H)-one 284
362.09 (E,5S,8aS)-2-(4-Brombenzyliden)-octahydro-6-hydroxy-5,8a-
2.77 362.09 dimethylnaphthalen-1(2H)-one 285 287.19
(E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-[(1-methyl- 2.84
287.20 1H-pyrrol-2-yl)methylen]naphthalen-1(2H)-one 286 312.21
(3E,4aS,5S)-4,4a,5,6,7,8-Hexahydro-5-hydroxy-4a-methyl-3- 2.69
312.21 {[(R)-4-(prop-1-en-2-yl)cyclohex-1-enyl]methylen}naphthalen-
2(3H)-one 287 258.13
(3E,4aS,5S)-3-[(Furan-3-yl)methylen]-4,4a,5,6,7,8-hexahydro- 2.75
258.11 5-hydroxy-4a-methylnaphthalen-2(3H)-one 288 376.18
(3E,4aS,5S)-3-(3-Fluorbenzyliden)-4a-benzyl-4,4a,5,6,7,8- 2.91
376.18 hexahydro-5-hydroxy-1-methylnaphthalen-2(3H)-one 289 308.18
(3E,4R,4aS,5S)-4a-Allyl-3-benzyliden-4,4a,5,6,7,8- 2.83 308.17
hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)-one 290 374.21
(E,5S,8aS)-2-(2,3,4-Trimethoxy-benzyliden)-octahydro-6- 2.96 374.21
hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 291 330.17
(E,5S,8aS)-2-(4-(Methylthio)-benzyliden)-octahydro-6- 2.74 330.17
hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 292 264.21
(E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-(2-methyl- 2.31
264.20 butyliden)naphthalen-1(2H)-one 293 410.07
(E,5S,8aS)-2-(2-Iodbenzyliden)-octahydro-6-hydroxy-5,8a- 2.82
410.09 dimethylnaphthalen-1(2H)-one 294 318.14
(E,5S,8aS)-2-(3-Chlorbenzyliden)-octahydro-6-hydroxy-5,8a- 2.74
318.15 dimethylnaphthalen-1(2H)-one 295 328.24
(2E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-{[(S)-4- 2.68
328.24 (prop-1-en-2-yl)cyclohex-1-enyl]methylen}naphthalen-1(2H)-
one 296 274.16
(E,5S,8aS)-2-[(Furan-2-yl)methylen]-octahydro-6-hydroxy- 2.72
274.16 5,8a-dimethylnaphthalen-1(2H)-one 297 328.24
(2E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-[(2,6,6- 2.46
328.23 trimethylcyclohexa-1,3-dienyl)-methylen]naphthalen-1(2H)-on
298 278.22
(E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-(2-methyl- 2.28
278.22 pentyliden)naphthalen-1(2H)-one 299 328.17
4-{(E)-[(1S,4aS)-Octahydro-2-hydroxy-1,4a-dimethyl-5-oxo- 2.94
328.15 naphthalen-6(1H)-yliden]methyl}benzoic acid 300 410.07
(E,5S,8aS)-2-(3-Iodbenzyliden)-octahydro-6-hydroxy-5,8a- 2.78
410.06 dimethylnaphthalen-1(2H)-one 301 302.17
(E,5S,8aS)-2-(3-Fluorbenzyliden)-octahydro-6-hydroxy-5,8a- 2.69
302.18 dimethylnaphthalen-1(2H)-one 302 236.18
(E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-propyliden- 2.27
236.19 naphthalen-1(2H)-one 303 374.13
(E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-(perfluor- 2.51
374.12 benzyliden)naphthalen-1(2H)-one 304 362.09
(E,5S,8aS)-2-(2-Brombenzyliden)-octahydro-6-hydroxy-5,8a- 2.76
362.09 dimethylnaphthalen-1(2H)-one 305 222.16
(E,5S,8aS)-2-Ethyliden-octahydro-6-hydroxy-5,8a- 2.24 222.15
dimethylnaphthalen-1(2H)-one 306 264.21
(E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-(2-methyl- 2.32
264.22 butyliden)naphthalen-1(2H)-one 307 302.17
(E,5S,8aS)-2-(4-Fluorbenzyliden)-octahydro-6-hydroxy-5,8a- 2.65
302.17 dimethylnaphthalen-1(2H)-one 308 328.24
(2E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-{[(R)-4- 2.68
328.24 (prop-1-en-2-yl)cyclohex-1-enyl]-methylen}naphthalen-1(2H)-
one 309 288.17 (E,5S,8aS)-Octahydro-6-hydroxy-5,8a-dimethyl-2-[(5-
2.74 288.17 methylfuran-2-yl)methylen]naphthalen-1(2H)-one 310
447.35 (E,1S,8aS)-7-[2-(2-Cyclohexylethinyl)benzyliden]-6- 3.10
447.36 (butylamino)-decahydro-5,8a-dimethylnaphthalen-1-ol 311
561.49 (E,4aS)-6-[2-(Hexadec-1-inyl)benzyliden]-5-(butylamino)-
3.36 561.52 decahydro-1,4a-dimethylnaphthalen-2-ol 312 435.30
(1S,7E,8aS)-7-{2-[2-(Trimethylsilyl)ethinyl]benzyliden}-6- 2.89
435.29 (butylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-
dimethylnaphthalen-1-ol 313 459.29
(E,1S,8aS)-7-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-6- 3.07
459.28 (butylamino)-decahydro-5,8a-dimethylnaphthalen-1-ol 314
393.27 (1S,7E,8aS)-7-[2-(3-Methoxyprap-1-inyl)benzyliden]-6-(butyl-
2.82 393.28 amino)-1,2
3,4,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol 315 435.30
(1S,7E,8aS)-7-{2-[2-(Trimethylsilyl)ethinyl]-benzyliden}-6- 2.91
435.30 (butylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-
dimethylnaphthalen-1-ol 316 431.32
(1S,7E,8aS)-7-[2-(2-Cyclohexylethinyl)benzyliden]-6-(butyl- 2.84
431.32 amino)-1,2,3,4,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol
317 459.29 (E,4aS)-6-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-5-
2.96 459.28 (butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 318
445.33 (1S,7E,8aS)-7-[2-(2-Cyclohexylethinyl)benzyliden]-6- 2.74
445.33 (butylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethyl-
naphthalen-1-ol 319 409.31
(E,1S,8aS)-7-[2-(3-Methoxyprop-1-inyl)benzyliden]-6- 2.83 409.30
(butylamino)-decahydro-5,8a-dimethylnaphthalen-1-ol 320 422.33
(E,4aS)-6-{2-[3-(Dimethylamino)prop-1-inyl]benzyliden}-5- 2.96
422.33 (butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 321
445.33 (1S,7E,8aS)-7-[2-(Hex-1-inyl)-benzyliden]-6-(cyclohexyl-
2.85 445.32
amino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylnaphthalen- 1-ol 322
446.33 (1S,7E,8aS)-7-{2-[3-(Dimethylamino)prop-1-inyl]benzyliden}-
2.97 446.33 6-(cyclohexylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a-
dimethylnaphthalen-1-ol 323 475.38
(E,4aS)-6-[2-(Oct-1-inyl)benzyliden]-5-(cyclohexylamino)- 3.14
475.38 decahydro-1,4a-dimethylnaphthalen-2-ol 324 522.36
(1S,7E,8aS)-7-{2-[3-(Dimethylamino)prop-1-inyl]benzyliden}- 3.30
522.37 8a-benzyl-6-(cyclohexylamino)-1,2,3,4,6,7,8,8a-octahydro-5-
methylnaphthalen-1-ol 325 386.17
(3E,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a, 2.94
386.18 5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one
326 528.40
(3E,4R,4aS,5S)-3-[2-(Hexadec-1-inyl)benzyliden]-4a-allyl-4, 3.27
528.39 4a,5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-2(3H)on
327 352.20
(E,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]-octahydro- 2.81
352.19 5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 328 365.24
(E,8aS)-2-{2-[3-(Dimethylamino)prop-1-inyl]benzyliden}- 2.87 365.24
octahydro-6-hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 329 400.18
(3E,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a, 2.84
400.18 5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-
one
330 350.19 (3E,4R,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]-
2.91 350.20
4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-dimethylnaphthalen- 2(3H)-one
331 402.20 (E,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-
2.96 402.19 octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one
332 488.37
(3E,4aS,5S)-3-[2-(Hexadec-1-inyl)benzyliden]-4,4a,5,6,7,8- 3.18
488.37 hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 333 426.20
(3E,4R,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4a- 3.21
426.21 allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-
2(3H)-one 334 336.17
(3E,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]- 2.86 336.16
4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen- 2(3H)-one 335
400.18 (3E,4R,4aS,5S)-3-{2-[2-(3-Fluorphenyl)ethinyl]benzyliden}-
2.82 400.18
4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-dimethylnaphthalen- 2(3H)-one
336 364.24
(E,8aS)-2-[2-(Hex-1-inyl)benzyliden]-octahydro-6-hydroxy- 2.79
364.25 5,8a-dimethylnaphthalen-1(2H)-one 337 350.19
(3E,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]- 2.83 350.20
4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen- 2(3H)-one
338 426.22 (3E,4aS,5S)-3-[2-(3-Methoxyprop-1-inyl)benzyliden]-4a-
3.26 426.22 benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-
methylnaphthalen-2(3H)-one 339 469.33
(1S,6E,7E,8S,8aS)-7-[3-(2-Cyclohexylethinyl)benzyliden]-8a- 3.09
469.34 allyl-6-(butylimino)-1,2,3,4,6,7,8,8a-octahydro-8-
methylnaphthalen-1-ol 340 409.30
(E,4aS)-6-[3-(3-Methoxyprop-1-inyl)benzyliden]-5- 2.93 409.30
(butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 341 423.31
(E,4aS)-6-[3-(3-Hydroxy-3-methylbut-1-inyl)benzyliden]-5- 3.11
423.32 (butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 342
429.30 (1S,7E,8aS)-7-[3-(2-Cyclohexylethinyl)benzyliden]-6-(butyl-
2.84 429.31
amino)-1,2,3,4,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol 343
459.29 (E,4aS)-6-{3-[2-(2-Fluorphenyl)ethinyl]benzyliden}-5- 2.89
459.30 (butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 344
421.33 (E,4aS)-6-[3-(Hex-1-inyl)benzyliden]-5-(butylamino)-deca-
2.77 421.33 hydro-1,4a-dimethylnaphthalen-2-ol 345 409.30
(E,1S,8aS)-7-[3-(3-Methoxyprop-1-inyl)benzyliden]-6- 2.83 409.29
(butylamino)-decahydro-5,8a-dimethylnaphthalen-1-ol 346 435.31
(E,1S,8aS)-7-[3-(3-Methoxyprop-1-inyl)benzyliden]-6- 2.87 435.31
(cyclohexylamino)-decahydro-5,8a-dimethylnaphthalen-1-ol 347 525.34
(E,1S,8S,8aR)-7-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-8a- 3.08
525.34 allyl-6-(cyclohexylamino)-decahydro-5,8-dimethylnaphthalen-
1-ol 348 386.17
(3E,4aS,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4,4a,5, 2.72
386.17 6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 349
392.24 (E,4R,4aR,5S)-3-[3-(3-Methoxyprop-1-inyl)benzyliden]-4a-
3.06 392.23
allyl-octahydro-5-hydroxy-1,4-dimethylnaphthalen-2(1H)-one 350
400.18 (3E,4aS,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}- 2.92
400.19 4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-
2(3H)-one 351 352.20
(E,8aS)-2-[3-(3-Methoxyprop-1-inyl)benzyliden]-octahydro-6- 2.86
352.19 hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 352 402.20
(E,4aS,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}- 2.85 402.21
octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 353 442.23
(E,4R,4aR,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4a- 3.04
442.23 allyl-octahydro-5-hydroxy-1,4-dimethylnaphthalen-2(1H)-one
354 336.17
(3E,4aS,5S)-3-[3-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6, 2.78
336.17 7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 355
502.38 (3E,4aS,5S)-3-[3-(Hexadec-1-inyl)benzyliden]-4,4a,5,6,7,8-
3.25 502.38 hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-one
356 400.18
(3E,4R,4aS,5S)-3-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}- 2.85
400.19 4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-
2(3H)-one 357 350.19
(3E,4aS,5S)-3-[3-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6, 2.84
350.19 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-on 358
426.22 (3E,4aS,5S)-3-[3-(3-Methoxyprop-1-inyl)benzyliden]-4a- 3.16
426.22 benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-
methylnaphthalen-2(3H)-one 359 409.30
(E,1S,8aS)-7-[3-(3-Methoxyprop-1-inyl)benzyliden]-6- 2.91 409.31
(butylamino)-decahydro-5,8a-dimethylnaphthalen-1-ol 360 447.35
(E,1S,8aS)-7-[3-(2-Cyclohexylethinyl)benzyliden]-6- 2.86 447.34
(butylamino)-decahydro-5,8a-dimethylnaphthalen-1-ol 361 409.30
(E,4aS)-6-[3-(3-Methoxyprop-1-inyl)benzyliden]-5- 2.94 409.29
(butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 362 499.30
(E,1S,8S,8aR)-7-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-8a- 3.20
499.30 allyl-6-(butylamino)-decahydro-5,8-dimethylnaphthalen-1-ol
363 423.31
(E,4aS)-6-[3-(3-Hydroxy-3-methylbut-1-inyl)benzyliden]-5- 3.03
423.29 (butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 364
431.32 (1S,7E,8aS)-7-[3-(2-Cyclohexylethinyl)benzyliden]-6-(butyl-
2.92 431.33
amino)-1,2,3,4,6,7,8,8a-octahydro-8a-methylnaphthalen-1-ol 365
459.29 (E,4aS)-6-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-5- 3.04
459.28 (butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 366
407.28 (1S,7E,8aS)-7-[3-(3-Hydroxy-3-methylbut-1-inyl)benzyliden]-
3.22 407.27 6-(butylamino)-1,2,3,4,6,7,8,8a-octahydro-8a-
methylnaphthalen-1-ol 367 449.33
(E,1S,8S,8aR)-7-[3-(3-Methoxyprop-1-inyl)benzyliden]-8a- 3.18
449.33 allyl-6-(butylamino)-decahydro-5,8-dimethylnaphthalen-1-ol
368 422.33
(E,4aS)-6-{3-[3-(Dimethylamino)prop-1-inyl]benzyliden}-5- 2.97
422.32 (butylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 369
485.31 (E,4aS)-6-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-5- 3.12
485.30 (cyclohexylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 370
559.33 (1S,7E,8aS)-7-{3-[2-(3-Fluorphenyl)ethinyl]benzyliden}-8a-
3.26 559.33
benzyl-6-(cyclohexylamino)-1,2,3,4,6,7,8,8a-octahydro-5-
methylnaphthalen-1-ol 371 435.31
(E,4aS)-6-[3-(3-Methoxyprop-1-inyl)benzyliden]-5-(cyclohexyl- 2.84
435.32 amino)-decahydro-1,4a-dimethylnaphthalen-2-ol 372 473.37
(E,4aS)-6-[3-(2-Cyclohexylethinyl)benzyliden]-5-(cyclohexyl- 2.81
473.38 amino)-decahydro-1,4a-dimethylnaphthalen-2-ol 373 431.32
(E,4aS)-6-[3-(3-Methylbut-3-en-1-inyl)benzyliden]-5- 2.86 431.32
(cyclohexylamino)-decahydro-1,4a-dimethylnaphthalen-2-ol 374 386.17
(3E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}- 2.91 386.17
4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen- 2(3H)-one 375
352.20 (E,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-octahydro-
2.96 352.20 5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 376 363.22
(3E,4R,4aS,5S)-3-{4-[3-(Dimethylamino)prop-1- 2.87 363.22
inyl]benzyliden}-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-
dimethylnaphthalen-2(3H)-one 377 376.20
(3E,4R,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-4a- 3.08
376.19 allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-
2(3H)-one 378 400.18
(3E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}- 2.96 400.18
4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen- 2(3H)-one
379 476.22
(3E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}-4a- 3.16
476.21 benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-
methylnaphthalen-2(3H)-one 380 414.26
(3E,4R,4aS,5S)-3-[4-(2-Cyclohexylethinyl)benzyliden]-4a- 3.07
414.26 allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen-
2(3H)-one 381 402.20
(E,4aS,5S)-3-{4-[2-(3-Fluorphenyl)ethinyl]benzyliden}- 2.87 402.20
octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one 382 402.26
(3E,4R,4aS,5S)-3-[4-(3-Cyclohexylprop-1-inyl)benzyliden]- 2.81
402.25 4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-
2(3H)-one 383 336.17
(3E,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6, 2.89
336.17 7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one 384
402.20
(E,8aS)-2-{4-[2-(3-Fluorphenyl)-ethinyl]benzyliden}-octahydro- 2.76
402.21 6-hydroxy-5,8a-dimethylnaphthalen-1(2H)-one 385 350.19
(3E,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-4,4a,5,6, 2.89
350.18 7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-on 386
426.22 (3E,4aS,5S)-3-[4-(3-Methoxyprop-1-inyl)benzyliden]-4a- 3.21
426.23 benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-
methylnaphthalen-2(3H)-one 387 389.24
(3E,4R,4aS,5S)-3-{4-[3-(Dimethylamino)prop-1- 3.07 389.23
inyl]benzyliden}-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-
methylnaphthalen-2(3H)-one 388 251.22
(1S,8aS)-6-(Diethylamino)-1,2,3,4,6,7,8,8a-octahydro-5,8a- 2.72
251.22 dimethylnaphthalen-1-ol 389 251.22
(1S,8S,8aS)-6-(Diethylamino)-1,2,3,4,6,7,8,8a-octahydro- 2.74
251.22 8,8a-dimethylnaphthalen-1-ol 390 237.21
(1S,8aS)-6-(Diethylamino)-1,2,3,4,6,7,8,8a-octahydro-8a- 2.69
237.20 methylnaphthalen-1-ol 391 327.26
(1S,8aR)-8a-Benzyl-6-(diethylamino)-1,2,3,4,6,7,8,8a- 2.85 327.28
octahydro-5-methylnaphthalen-1-ol 392 277.24
(1S,8S,8aS)-8a-Allyl-6-(diethylamino)-1,2,3,4,6,7,8,8a- 2.83 277.24
octahydro-8-methylnaphthalen-1-ol 393
(6E,4aS)-2-Furan-2-ylmethylene-5,8a-dimethyl-6-methylene-
3,4,6,7,8,8a-hexahydro-2H-naphthalen-1-one 394
2-Furan-2-ylmethylene-8-methyl-3,4,4a,5,8,8a-hexahydro-2H-
naphthalen-1-one 395
(4aS,5S)-5-Hydroxy-1,4a-dimethyl-3-(4-pyridin-4-ylethynyl-
benzylidene)-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-one 396
(4aS,5S)-3-[4-(3-Dimethylamino-prop-1-ynyl)-benzylidene]-5-
hydroxy-1,4a-dimethyl-4,4a,5,6,7,8-hexahydro-3H- naphthalen-2-one
397 (4aS,5S)-5-Hydroxy-1,4a-dimethyl-1-(3-phenyl-propyl)-
octahydro-naphthalen-2-one 398
(4aS,5S)-5-Hydroxy-1-(3-iodo-benzyl)-1,4a-dimethyl-
octahydro-naphthalen-2-one 399
(4aS,5S)-3-(4-Cyclohexylamino-benzylidene)-5-hydroxy-1,4a-
dimethyl-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-one 400
(4aS)-5,8a-Dimethyl-7-(5-methyl-furan-2-ylmethylene)-
hexahydro-naphthalen-1,6-dione 401
(2E,4aS)-5-(1,4a-Dimethyl-5-oxo-4,4a,5,6,7,8-hexahydro-3H-
naphthalen-2-ylidene)-5H-furan-2-one 402
(7'E)-7'-(4-iodo-benzylidene)-5',8a'-dimethylhexahydro-5'-(2-
phenylethyl)-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-6'(5'H)- one
403 2-Furan-2-ylmethylene-3,4,4a,5,8,8a-hexahydro-2H-
naphthalen-1-one 404
(4aS)-7-Benzylidene-5,8a-dimethyl-hexahydro-naphthalen- 1,6-dione
405 (4aS,5S)-5-Hydroxy-1,4a-dimethyl-1-(2-nitro-benzyl)-
octahydro-naphthalen-2-one 406
(4aS,5S)-5-Hydroxy-1-isobutyl-1,4a-dimethyl-1-octahydro-
naphthalen-2-one 407
8-Methyl-3,4,4a,5,8,8a-hexahydro-2H-naphthalen-1-one 408
(3E,4aS)-5,8a-Dimethyl-7-(2,4,6-trimethoxy-benzylidene)-
3,4,8,8a-tetrahydro-2H,7H-naphthalen-1,6-dione 409
(3E,3'E,4aS,4a'S)-1,3-bis[5,8a-dimethyl-3,4,8,8a-tetrahydro-
2H,7H-naphthalen-1,6-dione]-benzene 410
(4aS)-5-Butyliminomethyl-8a-methyl-3,4,8,8a-tetrahydro-
2H,7H-naphthalen-1,6-dione 411
(2E,4aS,5S)-6-Ethylidene-5,8a-dimethyl-1,2,3,4,6,7,8,8a-
octahydro-naphthalen-1-ol 412
(4aS,5S)-5-Hydroxy-3-[1-(4-iodo-phenyl)-propyl]-1,4a-
dimethyl-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-one 413
(4aS,5S)-5-Hydroxy-1,4a-dimethyl-4,4a,5,6,7,8-hexahydro-
3H-naphthalen-2-one 414
(4aS,5S)-1-Butyl-5-hydroxy-1,4a-dimethyl-1-octahydro-
naphthalen-2-one 415
(5E)-5-(5',8a'-dimethyl-3',4',8',8a'-tetrahydro-2'H-spiro[1,3-
dioxolane-2,1'-naphthalen]-6'(7'H)-ylidene)furan-2(5H)-one 416
(7'E)-5'-(3,5-Dibromobenzyl)-7'-(4-iodo-benzylidene)-5',8a'-
dimethylhexahydro-2'H-spiro[1,3-dioxolane-2,1'-naphthalen]-
6'(5'H)-one 417
5-Hydroxy-7-isopropyl-1-methyl-4,4a,5,6,7,8,-hexahydro-3H-
naphthalen-2-one 418
(4aS,5S)-5-Hydroxy-1,4a-dimethyl-1-octahydro-naphthalen-2- one
[0025] The present invention also comprises pharmaceutically
acceptable salts of the compounds according to the general formula
(I), all stereoisomeric forms of the compounds according to the
general formula (I) as well as solvates, especially hydrates or
prodrugs thereof. A prodrug is commonly described as an inactive or
protected derivative of an active ingredient or a drug, which is
converted to the active ingredient or drug in the body.
[0026] In case, the inventive compounds bear basic and/or acidic
substituents, they may form salts with organic or inorganic acids
or bases. Examples of suitable acids for such acid addition salt
formation are hydrochloric acid, hydrobromic acid, sulfuric acid,
phosphoric acid, acetic acid, citric acid, oxalic acid, malonic
acid, salicylic acid, p-aminosalicylic acid, malic acid, fumaric
acid, succinic acid, ascorbic acid, maleic acid, sulfonic acid,
phosphonic acid, perchloric acid, nitric acid, formic acid,
propionic acid, gluconic acid, lactic acid, tartaric acid,
hydroxymaleic acid, pyruvic acid, phenylacetic acid, benzoic acid,
p-aminobenzoic acid, p-hydroxybenzoic acid, methanesulfonic acid,
ethanesulfonic acid, nitrous acid, hydroxyethanesulfonic acid,
ethylenesulfonic acid, p-toluenesulfonic acid, naphthylsulfonic
acid, sulfanilic acid, camphorsulfonic acid, china acid, mandelic
acid, o-methylmandelic acid, hydrogen-benzenesulfonic acid, picric
acid, adipic acid, d-o-tolyltartaric acid, tartronic acid, (o, m,
p)-toluic acid, naphthylamine sulfonic acid, and other mineral or
carboxylic acids well known to those skilled in the art. The salts
are prepared by contacting the free base form with a sufficient
amount of the desired acid to produce a salt in the conventional
manner. Examples for suitable inorganic or organic bases are, for
example, NaOH, KOH, NH.sub.4OH, tetraalkylammonium hydroxide,
lysine or arginine and the like. Salts may be prepared in a
conventional manner using methods well known in the art, for
example by treatment of a solution of the compound of the general
formula (I) with a solution of an acid, selected out of the group
mentioned above.
[0027] Some of the compounds of the present invention may be
crystallised or recrystallised from solvents such as aqueous and
organic solvents. In such cases solvates may be formed. This
invention includes within its scope stoichiometric solvates
including hydrates as well as compounds containing variable amounts
of water that may be produced by processes such as
lyophilisation.
[0028] Certain compounds of the general formula (I) may exist in
the form of optical isomers, e.g. diastereoisomers and mixtures of
isomers in all ratios, e.g. racemic mixtures. The invention
includes all such forms, in particular the pure isomeric forms. The
different isomeric forms may be separated or resolved one from the
other by conventional methods, or any given isomer may be obtained
by conventional synthetic methods or by stereospecific or
asymmetric syntheses. Where a compound according to the general
formula (I) contains an alkene moiety, the alkene can be presented
as a cis or trans isomer or a mixture thereof. When an isomeric
form of a compound of the invention is provided substantially free
of other isomers, it will preferably contain less than 5% w/w, more
preferably less than 2% w/w and especially less than 1% w/w of the
other isomers.
[0029] Another aspect of the present invention relates to the use
of the inventive decaline derivatives as drugs, i.d. as
pharmaceutically active agents applicable in medicine. Furthermore,
it was found that the decaline derivatives of the present invention
are inhibitors of kinases and phosphatases, especially of
11.beta.HSD1 (11.beta.-hydroxysteroid dehydrogenase type 1).
[0030] The 11.beta.HSD2 isoenzyme catalyzes exclusively the
oxidation of cortisol, and inhibition of 11.beta.HSD2 causes sodium
retention resulting in hypertension. Therefore
isoenzyme-specificity is a major prerequisite for the clinical use
of 11.beta.HSD1 inhibitors. 11.beta.HSD1 inhibitors can be applied
in the treatment of several diseases, such as the metabolic
syndrome, diabetes type 2, obesity and cognitive dysfunction.
Moreover, 11betaHSD1 inhibition slows down plaque progression in
the context of atherosclerosis (Hermanowski-Vosatka et al., The
Journal of Experimental Medicine, 2005, 202, 4, 517-527).
11betaHSD1 inhibition also offers a novel therapeutic approach to
improve healing of ischemic or injured tissue (Small et al., Proc.
Natl. Acad. Sci. U.S.A. 2005, 102, 34, 12165-12170). Within the
present decaline derivatives also inhibitors for a panel of
phosphatases including Cdc25A phosphatase, VHR, PTP1B, PP1 and
MtPTPA as well as for acetylcholinesterase could be identified.
[0031] Cdc25A is a dual-specificity phosphatase that regulates
progression of cell division at the G1.fwdarw.S checkpoint by
dephosphorylating Cdk2/cyclin complexes. Cdc25A is considered a
viable target in the development of new anti-tumor drugs. PTP1B
(protein tyrosine phosphatase 1B) is thought to function as a
negative regulator of insulin and leptin signal transduction.
Increased incidence of type 2 diabetes mellitus and obesity has
elevated the medical need for new agents to treat these disease
states. Resistance to the hormones insulin and leptin are hallmarks
of both type 2 diabetes and obesity. Drugs that can ameliorate this
resistance should be effective in treating type 2 diabetes and
possibly obesity. PTP1B can therefore be regarded as a novel target
for type 2 diabetes.
[0032] VHR affects the MAPK pathway by dephosphorylating ERK
(extracellular regulated kinase) 1 and ERK2 as well as JNK (c-Jun
N-terminal kinase), which leads in all three cases to their
inactivation. VHR is related to cellular proliferation and
inflammation processes.
[0033] PP1 is a Ser/Thr-phosphatase that plays an important role in
cellular proliferation and differentiation, since it can
dephosphorylate tumor suppressor protein Retinoblastoma (pRb) so
that transcription cannot take place. PP1 is considered an
interesting target in the treatment of various cancers.
[0034] MtPTPA (a protein tyrosine phosphatase of Mycobacterium
tuberculosis) seems to disturb phosphotyrosine-mediated signal
transduction in the immune system of the host organism and may
therefore represent a viable target in the treatment of
tuberculosis.
[0035] Acetylcholinesterase (AChE) hydrolyzes the neurotransmitter
acetylcholine and thereby terminates impulse transmission at
cholinergic synapses. AChE inhibitors are used in the treatment of
various disorders such as myasthenia gravis, glaucoma and
Alzheimer's disease.
[0036] Table II (cf. below) shows the half-maximal inhibition
concentration (IC.sub.50) values of representative compounds
according to general formula (I). Table II shows inhibition rates
with IC.sub.50 between 10 and 50 .mu.M and below 10 .mu.M. The
results exhibited table II prove that the compounds of the present
invention are potent pharmaceutically active agents against various
diseases that can be treated and/or prohibited by inhibition of the
targets {circle around (2)}-{circle around (9)}.
TABLE-US-00002 TABLE II Inhibitory effect of the compounds of the
present invention on different targets (a = 50 .mu.M > IC.sub.50
> 10 .mu.M & aa = IC.sub.50 < 10 .mu.M) {circle around
(1)} {circle around (2)} {circle around (3)} {circle around (4)}
{circle around (5)} {circle around (6)} {circle around (7)} {circle
around (8)} {circle around (9)} 1 a aa 3, 16, 27, 30, 33, 39, 43,
58, 79, a a 395, 406 7, 18, 20, 68, 89, 107, 115, 126, a 136, 138,
143, 146, 153, 190, 198, 202, 203, 205, 215, 223, 225, 241, 242,
266, 267, 286, 347, 362, 400, 402, 404, 405, 408, 409, 410 8, 9 aa
a a 60, 62, 393, 398 a a a 394 a aa a 19 aa 24 a a a a aa 25 a a a
26 a a a aa a 32 aa a a a aa aa aa aa 38, 46, 54 a a aa a 40, 44 a
a a a 56, 158, 396, 412, 413 a a a 45 a a aa 47 a a a aa 49 a aa aa
a 50, 55 a a aa a 51 a a aa 397 a a a 333, 401 a a 137, 138 a aa
125, 127, 128, 130, 131, 133, a a 134, 141 4 a a a aa 12 a a aa 17
a a 29 aa a aa aa aa 31 a aa a aa 34, 37, 41, 59, 61, 63, 66, 90, a
282, 417 53 a a a 64, 414 a a 83, 416 a aa 42, 91 aa 48, 67, 71,
72, 86, 323, 325, 326, a 332, 334, 335, 346, 349, 350, 353, 415 411
a 388 a 10, 11, 14, 22, 23, 73, 83, 85, 97, aa 98, 399, 407 15 aa a
65 a 403 aa aa 167 aa {circle around (1)} Compound Number {circle
around (2)} Target VHR {circle around (3)} Target PTP1B {circle
around (4)} Target Cdc25A {circle around (5)} Target PP1 {circle
around (6)} Target MPTPA {circle around (7)} Target 11beta-HSD1
{circle around (8)} Target 11beta-HSD2 {circle around (9)} Target
AChE
[0037] Thus, the decaline compounds of the present invention can be
used for prophylaxis and treatment of diabetes mellitus type I,
diabetes mellitus type II, tuberculosis, proliferative diseases,
cancer, infectious diseases, neurodegenerative diseases, obesity,
cognitive dysfunctions, metabolic syndromes or for the preparation
of a pharmaceutical formulation for prophylaxis and treatment of
diabetes mellitus type I, diabetes mellitus type II, tuberculosis,
proliferative diseases, cancer, infectious diseases,
neurodegenerative diseases, obesity, cognitive dysfunctions,
metabolic syndromes.
[0038] Examples for neurodegenerative diseases are Alzheimer
disease, Parkinson disease, Huntington disease, amyotrophic lateral
sclerosis, AIDS-related dementia, retinitis pigmentosa, spinal
muscular atrophy and cerebrellar degeneration, fragile X-associated
tremor/ataxia syndrome (FXTAS), progressive supranuclear palsy
(PSP), and striatonigral degeneration (SND), which is included with
olivopontocerebellear degeneration (OPCD), and Shy Drager syndrome
(SDS) in a syndrome known as multiple system atrophy (MSA).
Alzheimer disease and Parkinson disease are two mayor indications
for the decaline-derived compounds of the present invention.
[0039] Furthermore, the compounds of the present invention are
useful for the treatment of various cancer types such as
adenocarcinoma, choroidal melanoma, acute leukemia, acoustic
neurinoma, ampullary carcinoma, anal carcinoma, astrocytoma, basal
cell carcinoma, pancreatic cancer, desmoid tumor, bladder cancer,
bronchial carcinoma, breast cancer, Burkitt's lymphoma, corpus
cancer, CUP-syndrome (carcinoma of unknown primary), colorectal
cancer, small intestine cancer, small intestinal tumors, ovarian
cancer, endometrial carcinoma, ependymoma, epithelial cancer types,
Ewing's tumors, gastrointestinal tumors, gastric cancer,
gallbladder cancer, gall bladder carcinomas, uterine cancer,
cervical cancer, cervix, glioblastomas, gynecologic tumors, ear,
nose and throat tumors, hematologic neoplasias, hairy cell
leukemia, urethral cancer, skin cancer, skin testis cancer, brain
tumors (gliomas), brain metastases, testicle cancer, hypophysis
tumor, carcinoids, Kaposi's sarcoma, laryngeal cancer, germ cell
tumor, bone cancer, colorectal carcinoma, head and neck tumors
(tumors of the ear, nose and throat area), colon carcinoma,
craniopharyngiomas, oral cancer (cancer in the mouth area and on
lips), cancer of the central nervous system, liver cancer, liver
metastases, leukemia, eyelid tumor, lung cancer, lymph node cancer
(Hodgkin's/Non-Hodgkin's), lymphomas, stomach cancer, malignant
melanoma, malignant neoplasia, malignant tumors gastrointestinal
tract, breast carcinoma, rectal cancer, medulloblastomas, melanoma,
meningiomas, Hodgkin's disease, mycosis fungoides, nasal cancer,
neurinoma, neuroblastoma, kidney cancer, renal cell carcinomas,
non-Hodgkin's lymphomas, oligodendroglioma, esophageal carcinoma,
osteolytic carcinomas and osteoplastic carcinomas, osteosarcomas,
ovarial carcinoma, pancreatic carcinoma, penile cancer,
plasmocytoma, prostate cancer, pharyngeal cancer, rectal carcinoma,
retinoblastoma, vaginal cancer, thyroid carcinoma, Schneeberger
disease, esophageal cancer, spinalioms, T-cell lymphoma (mycosis
fungoides), thymoma, tube carcinoma, eye tumors, urethral cancer,
urologic tumors, urothelial carcinoma, vulva cancer, wart
appearance, soft tissue tumors, soft tissue sarcoma, Wilm's tumor,
cervical carcinoma and tongue cancer.
[0040] Most active are the inventive compounds on lung cancer,
lymph node cancer (Hodgkin's/Non-Hodgkin's), head and neck tumors
(tumors of the ear, nose and throat area), breast cancer, ovarian
cancer, gastric cancer, gastrointestinal tumors, intestinal
tumors.
[0041] Furthermore, the compounds of the general formulas disclosed
herein were identified as angiogenesis inhibitors which are useful
for cancer treatment by blocking the formation of vessels into the
tumor or tumorous tissue.
[0042] Also infectious diseases including opportunistic diseases
can be treated by the decaline-derived compounds of the present
invention. Such infectious diseases comprise for instance AIDS,
Alveolar Hydatid Disease (AHD, Echinococcosis), Amebiasis
(Entamoeba histolytica Infection), Angiostrongylus Infection,
Anisakiasis, Anthrax, Babesiosis (Babesia Infection), Balantidium
Infection (Balantidiasis), Baylisascaris Infection (Raccoon
Roundworm), Bilharzia (Schistosomiasis), Blastocystis hominis
Infection (Blastomycosis), Boreliosis, Botulism, Brainerd Diarrhea,
Brucellosis, BSE (Bovine Spongiform Encephalopathy), Candidiasis,
Capillariasis (Capillaria Infection), CFS (Chronic Fatigue
Syndrome), Chagas Disease (American Trypanosomiasis), Chickenpox
(Varicella-Zoster virus), Chlamydia pneumoniae Infection, Cholera,
Chronic Fatigue Syndrome, CJD (Creutzfeldt-Jakob Disease),
Clonorchiasis (Clonorchis Infection), CLM (Cutaneous Larva Migrans,
Hookworm Infection), Coccidioidomycosis, Conjunctivitis,
Coxsackievirus A16 (Hand, Foot and Mouth Disease), Cryptococcosis,
Cryptosporidium Infection (Cryptosporidiosis), Culex mosquito
(Vector of West Nile Virus), Cutaneous Larva Migrans (CLM),
Cyclosporiasis (Cyclospora Infection), Cysticercosis
(Neurocysticercosis), Cytomegalovirus Infection, Dengue/Dengue
Fever, Ebola Virus Hemorrhagic Fever, Echinococcosis (Alveolar
Hydatid Disease), Encephalitis, Entomoeba coli Infection, Entomoeba
dispar Infection, Entomoeba hartmanni Infection, Entomoeba
histolytica Infection (Amebiasis), Entomoeba polecki Infection,
Enterobiasis (Pinworm Infection), Enterovirus Infection
(Non-Polio), Epstein-Barr Virus Infection, Escherichia coli
Infection, Foodborne Infection, Foot and mouth Disease, Fungal
Dermatitis, Gastroenteritis, Group A streptococcal Disease, Group B
streptococcal Disease, Hansen's Disease (Leprosy), Hantavirus
Pulmonary Syndrome, Helicobacter pylori Infection, Hematologic
Disease, Hendra Virus Infection, Hepatitis (HCV, HBV), Herpes
Zoster (Shingles), HIV Infection, Human Ehrlichiosis, Human
Parainfluenza Virus Infection, Influenza, Isosporiasis (Isospora
Infection), Lassa Fever, Leishmaniasis, Kala-azar (Kala-azar,
Leishmania Infection), Leprosy, Lice (Body lice, Head lice, Pubic
lice), Lyme Disease, Malaria, Marburg Hemorrhagic Fever, Measles,
Meningitis, Mosquito-borne Diseases, Mycobacterium avium Complex
(MAC) Infection, Naegleria Infection, Nosocomial Infections,
Nonpathogenic Intestinal Amebae Infection, Onchocerciasis (River
Blindness), Opisthorciasis (Opisthorcis Infection), Parvovirus
Infection, Plague, PCP (Pneumocystis carinii Pneumonia), Polio, Q
Fever, Rabies, Respiratory Syncytial Virus (RSV) Infection,
Rheumatic Fever, Rift Valley Fever, River Blindness
(Onchocerciasis), Rotavirus Infection, Roundworms Infection,
Salmonellosis, Salmonella Enteritidis, Scabies, Shigellosis,
Shingles, Sleeping Sickness, Smallpox, Streptococcal Infection,
Tapeworm Infection (Taenia Infection), Tetanus, Toxic Shock
Syndrome, Tuberculosis, Ulcers (Peptic Ulcer Disease), Valley
Fever, Vibrio parahaemolyticus Infection, Vibrio vulnificus
Infection, Viral Hemorrhagic Fever, Warts, Waterborne infectious
Diseases, West Nile Virus Infection (West Nile Encephalitis),
Whooping Cough, Yellow Fever, tuberculosis, leprosy,
mycobacteria-induced meningitis.
[0043] Especially tuberculosis is one important indication for the
present compounds.
[0044] Further indications are cognitive disorders. The term
"cognitive disorder" shall refer to anxiety disorders, delirium,
dementia, amnestic disorders, dissociative disorders, eating
disorders, mood disorders, schizophrenia, psychotic disorders,
sexual and gender identity disorders, sleep disorders, somatoform
disorders, acute stress disorder, obsessive-compulsive disorder,
panic disorder, posttraumatic stress disorder, specific phobia,
social phobia, substance withdrawal delirium, Alzheimer's disease,
Creutzfeldt-Jakob disease, head trauma, Huntington's disease, HIV
disease, Parkinson's disease, Pick's disease, learning disorders,
motor skills disorders, developmental coordination disorder,
communication disorders, phonological disorder, pervasive
developmental disorders, Asperger's disorder, autistic disorder,
childhood disintegrative disorder, Rett's disorder, pervasive
developmental disorder, attention-deficit/hyperactivity disorder
(ADHD), conduct disorder, oppositional defiant disorder, pica,
rumination disorder, tic disorders, chronic motor or vocal tic
disorder, Tourette's disorder, elimination disorders, encopresis,
enuresis, selective mutism, separation anxiety disorder,
dissociative amnesia, depersonalization disorder, dissociative
fugue, dissociative identity disorder, anorexia nervosa, bulimia
nervosa, bipolar disorders, schizophreniform disorder,
schizoaffective disorder, delusional disorder, psychotic disorder,
shared psychotic disorder, delusions, hallucinations,
substance-induced psychotic disorder, orgasmic disorders, sexual
pain disorders, dyspareunia, vaginismus, sexual dysfunction,
paraphilias, dyssomnias, breathing-related sleep disorder,
circadian rhythm sleep disorder, hypersomnia, insomnia, narcolepsy,
dyssomnia, parasomnias, nightmare disorder, sleep terror disorder,
sleepwalking disorder, parasomnia, body dysmorphic disorder,
conversion disorder, hypochondriasis, pain disorder, somatization
disorder, alcohol related disorders, amphetamine related disorders,
caffeine related disorders, cannabis related disorders, cocaine
related disorders, hallucinogen related disorders, inhalant related
disorders, nicotine related disorders, opioid related disorders,
phencyclidine-related disorder, abuse, persisting amnestic
disorder, intoxication, withdrawal.
[0045] It was also found that the compounds disclosed herein are
useful for the treatment and prophylaxis of the Cushing's syndrome
and Addison's disease two very serious, potentially lethal clinical
disorders, which are related to glucocorticoid excess or deficiency
(glucocorticoid dysfunction) as well as diseases which are caused
or induced by disorders or dysfunction of the glucocorticoid
signaling cascade. Such diseases are, for instance, glucocorticoid
hypersensitivity, glucocorticoid resistance, hypercortisolism,
obesity, the dysmetabolic syndrome, diabetes type 2, melancholic
depression, osteoporosis, anxiety, insomnia, asthenia, depression,
memory dysfunction, executive dysfunction, fatigue, hyperalgesia,
poor quality sleep, insulin resistance, atrophy (sarcopenia),
growth stunting, hypertension.
[0046] Another aspect of the present invention is directed to the
use of at least one compound of any one of the general formulas
disclosed herein and/or pharmaceutically acceptable salts thereof
for prophylaxis and/or treatment of cardiovascular diseases,
cardiovascular disorders and metabolic syndromes.
[0047] The metabolic syndrome is a cluster of cardiovascular risk
factors, including visceral obesity, insulin resistance,
dyslipidemia, obesity, hypertension, impaired glucose tolerance and
hypertriglyceridemia.
[0048] Examples of cardiovascular diseases and disorders are: adult
congenital heart disease, aneurysm, stable angina, unstable angina,
angina pectoris, angioneurotic edema, aortic valve stenosis, aortic
aneurysm, arrhythmia, arrhythmogenic right ventricular dysplasia,
arteriosclerosis, atherosclerosis, arteriovenous malformations,
atrial fibrillation, Behcet syndrome, bradycardia, cardiac
tamponade, cardiomegaly, congestive cardiomyopathy, hypertrophic
cardiomyopathy, restrictive cardiomyopathy, cardiovascular disease
prevention, carotid stenosis, cerebral hemorrhage, Churg-Strauss
syndrome, diabetes, Ebstein's Anomaly, Eisenmenger complex,
cholesterol embolism, bacterial endocarditis, fibromuscular
dysplasia, congenital heart defects, heart diseases, congestive
heart failure, heart valve diseases, heart attack, epidural
hematoma, hematoma, subdural, Hippel-Lindau disease, hyperemia,
hypertension, pulmonary hypertension, hypertrophic growth, left
ventricular hypertrophy, right ventricular hypertrophy, hypoplastic
left heart syndrome, hypotension, intermittent claudication,
ischemic heart disease, Klippel-Trenaunay-Weber syndrome, lateral
medullary syndrome, long QT syndrome mitral valve prolapse,
moyamoya disease, mucocutaneous lymph node syndrome, myocardial
infarction, myocardial ischemia, myocarditis, pericarditis,
peripheral vascular diseases, phlebitis, polyarteritis nodosa,
pulmonary atresia, Raynaud disease, restenosis, Sneddon syndrome,
stenosis, superior vena cava syndrome, syndrome X, tachycardia,
Takayasu's arteritis, hereditary hemorrhagic telangiectasia,
telangiectasis, temporal arteritis, tetralogy of fallot,
thromboangiitis obliterans, thrombosis, thromboembolism, tricuspid
atresia, varicose veins, vascular diseases, vasculitis, vasospasm,
ventricular fibrillation, Williams syndrome, peripheral vascular
disease, varicose veins and leg ulcers, deep vein thrombosis,
Wolff-Parkinson-White syndrome.
[0049] Another important aspect of the present invention deals with
the use of the decaline-derived compounds in combination with
common drugs such as anti-HIV drugs, antiproliferative drug,
cytotoxic or cytostatic drug, ganciclovir, foscarnet, cidofovir,
valganciclovir, fomivirsen, penciclovir or valaciclovir. In some
cases, the inventive compounds are able to increase the activity of
the common drugs and/or reduce their undesired side effects.
[0050] Therefore, another aspect of the present invention is
directed to pharmaceutical compositions comprising at least one
compound of the present invention as active ingredient, together
with at least one pharmaceutically acceptable carrier, excipient
and/or diluents. The pharmaceutical compositions of the present
invention can be prepared in a conventional solid or liquid carrier
or diluent and a conventional pharmaceutically-made adjuvant at
suitable dosage level in a known way. The preferred preparations
are adapted for oral application. These administration forms
include, for example, pills, tablets, film tablets, coated tablets,
capsules, powders and deposits.
[0051] Furthermore, the present invention also includes
pharmaceutical preparations for parenteral application, including
dermal, intradermal, intragastral, intracutan, intravasal,
intravenous, intramuscular, intraperitoneal, intranasal,
intravaginal, intrabuccal, percutan, rectal, subcutaneous,
sublingual, topical, or transdermal application, which preparations
in addition to typical vehicles and/or diluents contain at least
one compound according to the present invention and/or a
pharmaceutical acceptable salt thereof as active ingredient.
[0052] The pharmaceutical compositions according to the present
invention containing at least one compound according to the present
invention, and/or a pharmaceutical acceptable salt thereof as
active ingredient will typically be administered together with
suitable carrier materials selected with respect to the intended
form of administration, i.e. for oral administration in the form of
tablets, capsules (either solid filled, semi-solid filled or liquid
filled), powders for constitution, extrudates, deposits, gels,
elixirs, dispersable granules, syrups, suspensions, and the like,
and consistent with conventional pharmaceutical practices. For
example, for oral administration in the form of tablets or
capsules, the active drug component may be combined with any oral
non-toxic pharmaceutically acceptable carrier, preferably with an
inert carrier like lactose, starch, sucrose, cellulose, magnesium
stearate, dicalcium phosphate, calcium sulfate, talc, mannitol,
ethyl alcohol (liquid filled capsules) and the like. Moreover,
suitable binders, lubricants, disintegrating agents and coloring
agents may also be incorporated into the tablet or capsule. Powders
and tablets may contain about 5 to about 95 weight % of the
decalin-derived compound and/or the respective pharmaceutically
active salt as active ingredient.
[0053] Suitable binders include starch, gelatin, natural sugars,
corn sweeteners, natural and synthetic gums such as acacia, sodium
alginate, carboxymethylcellulose, polyethylene glycol and waxes.
Among suitable lubricants there may be mentioned boric acid, sodium
benzoate, sodium acetate, sodium chloride, and the like. Suitable
disintegrants include starch, methylcellulose, guar gum, and the
like. Sweetening and flavoring agents as well as preservatives may
also be included, where appropriate. The disintegrants, diluents,
lubricants, binders etc. are discussed in more detail below.
[0054] Moreover, the pharmaceutical compositions of the present
invention may be formulated in sustained release form to provide
the rate controlled release of any one or more of the components or
active ingredients to optimise the therapeutic effect(s), e.g.
antihistaminic activity and the like. Suitable dosage forms for
sustained release include tablets having layers of varying
disintegration rates or controlled release polymeric matrices
impregnated with the active components and shaped in tablet form or
capsules containing such impregnated or encapsulated porous
polymeric matrices.
[0055] Liquid form preparations include solutions, suspensions, and
emulsions. As an example, there may be mentioned water or
water/propylene glycol solutions for parenteral injections or
addition of sweeteners and opacifiers for oral solutions,
suspensions, and emulsions. Liquid form preparations may also
include solutions for intranasal administration. Aerosol
preparations suitable for inhalation may include solutions and
solids in powder form, which may be present in combination with a
pharmaceutically acceptable carrier such as an inert, compressed
gas, e.g. nitrogen. For preparing suppositories, a low melting fat
or wax, such as a mixture of fatty acid glycerides like cocoa
butter is melted first, and the active ingredient is then dispersed
homogeneously therein e.g. by stirring. The molten, homogeneous
mixture is then poured into conveniently sized moulds, allowed to
cool, and thereby solidified,
[0056] Also included are solid form preparations which are intended
to be converted, shortly before use, to liquid form preparations
for either oral or parenteral administration. Such liquid forms
include solutions, suspensions, and emulsions.
[0057] The compounds according to the present invention may also be
delivered transdermally. The transdermal compositions may have the
form of a cream, a lotion, an aerosol and/or an emulsion and may be
included in a transdermal patch of the matrix or reservoir type as
is known in the art for this purpose.
[0058] The term capsule as recited herein refers to a specific
container or enclosure made e.g. of methyl cellulose, polyvinyl
alcohols, or denatured gelatins or starch for holding or containing
compositions comprising the active ingredient(s). Capsules with
hard shells are typically made of blended of relatively high gel
strength gelatins from bones or pork skin. The capsule itself may
contain small amounts of dyes, opaquing agents, plasticisers and/or
preservatives. Under tablet a compressed or moulded solid dosage
form is understood which comprises the active ingredients with
suitable diluents. The tablet may be prepared by compression of
mixtures or granulations obtained by wet granulation, dry
granulation, or by compaction well known to a person of ordinary
skill in the art.
[0059] Oral gels refer to the active ingredients dispersed or
solubilised in a hydrophilic semi-solid matrix. Powders for
constitution refers to powder blends containing the active
ingredients and suitable diluents which can be suspended e.g. in
water or in juice.
[0060] Suitable diluents are substances that usually make up the
major portion of the composition or dosage form. Suitable diluents
include sugars such as lactose, sucrose, mannitol, and sorbitol,
starches derived from wheat, corn rice, and potato, and celluloses
such as microcrystalline cellulose. The amount of diluent in the
composition can range from about 5 to about 95% by weight of the
total composition, preferably from about 25 to about 75 weight %,
and more preferably from about 30 to about 60 weight %.
[0061] The term disintegrants refers to materials added to the
composition to support break apart (disintegrate) and release the
pharmaceutically active ingredients of a medicament. Suitable
disintegrants include starches, "cold water soluble" modified
starches such as sodium carboxymethyl starch, natural and synthetic
gums such as locust bean, karaya, guar, tragacanth and agar,
cellulose derivatives such as methylcellulose and sodium
carboxymethylcellulose, microcrystalline celluloses, and
cross-linked microcrystalline celluloses such as sodium
croscaramellose, alginates such as alginic acid and sodium
alginate, clays such as bentonites, and effervescent mixtures. The
amount of disintegrant in the composition may range from about 2 to
about 20 weight % of the composition, more preferably from about 5
to about 10 weight %.
[0062] Binders are substances which bind or "glue" together powder
particles and make them cohesive by forming granules, thus serving
as the "adhesive" in the formulation. Binders add cohesive strength
already available in the diluent or bulking agent. Suitable binders
include sugars such as sucrose, starches derived from wheat corn
rice and potato, natural gums such as acacia, gelatin and
tragacanth, derivatives of seaweed such as alginic acid, sodium
alginate and ammonium calcium alginate, cellulose materials such as
methylcellulose, sodium carboxymethylcellulose and
hydroxypropylmethylcellulose, polyvinylpyrrolidone, and inorganic
compounds such as magnesium aluminum silicate. The amount of binder
in the composition may range from about 2 to about 20 weight % of
the composition, preferably from about 3 to about 10 weight %, and
more preferably from about 3 to about 6 weight %.
[0063] Lubricants refer to a class of substances which are added to
the dosage form to enable the tablet granules etc. after being
compressed to release from the mould or die by reducing friction or
wear. Suitable lubricants include metallic stearates such as
magnesium stearate, calcium stearate, or potassium stearate,
stearic acid, high melting point waxes, and other water soluble
lubricants such as sodium chloride, sodium benzoate, sodium
acetate, sodium oleate, polyethylene glycols and D,L-leucine.
Lubricants are usually added at the very last step before
compression, since they must be present at the surface of the
granules. The amount of lubricant in the composition may range from
about 0.2 to about 5 weight % of the composition, preferably from
about 0.5 to about 2 weight %, and more preferably from about 0.3
to about 1.5 weight % of the composition.
[0064] Glidents are materials that prevent caking of the components
of the pharmaceutical composition and improve the flow
characteristics of granulate so that flow is smooth and uniform.
Suitable glidents include silicon dioxide and talc. The amount of
glident in the composition may range from about 0.1 to about 5
weight % of the final composition, preferably from about 0.5 to
about 2 weight %.
[0065] Coloring agents are excipients that provide coloration to
the composition or the dosage form. Such excipients can include
food grade dyes adsorbed onto a suitable adsorbent such as clay or
aluminum oxide. The amount of the coloring agent may vary from
about 0.1 to about 5 weight % of the composition, preferably from
about 0.1 to about 1 weight %.
DESCRIPTION OF FIGURES
[0066] FIG. 1 shows two important general subformula for two
important subgroup of compounds of the present invention having the
decaline scaffold,
[0067] FIG. 2 shows representative examples of the inventive
decaline-derived compounds,
[0068] FIG. 3 shows representative examples of the inventive
decaline-derived compounds.
EXPERIMENTAL PART
Analytical HPLC-MS Method
[0069] Analytical HPLC/MS was performed on:
1.) For Substance 1-158:
[0070] HP Model Hewlett Packard Series 1100 coupled to a Finnigan
MAT LCQ mass detector. UV spectra recording is integrated in the HP
Model Hewlett Packard Series 1100. UV spectra were recorded 210 and
254 nm.
[0071] Chromatography was performed using the parameters cited
below:
TABLE-US-00003 Solvents: Acetonitrile (Biosolve) Water (Millipore)
Column: Macherey&Nagel CC 125/4 Nucleosil 120-5 C4 Flow rate:
0.5 ml/min Gradient: A: Water/0.1% TFA B: Acetonitrile/0.1% TFA
Time A % B % 0.00 90 10 2.00 30 70 10.00 100 0
[0072] UV spectra were recorded at 210 and 254 nm with a sampling
rate of 0.5 spectra/second. Mass spectra were obtained using
positive and negative electrospray ionization over the range m/z 70
to 900. The scan rate was 0.5 scan (m/z 70 to 900) per second.
2.) For Substance 159-392:
[0073] Micromass LCT: HPLC Waters 600 coupled to a Micromass
TOF-MUX-Interface. UV spectra recording is integrated in the
Micromass LCT. UV spectra were recorded at 210 nm.
[0074] Chromatography was performed using the parameters cited
below:
TABLE-US-00004 Solvents: Acetonitrile (Biosolve) Water (Millipore)
Column: Phenomenex Synergi 2.mu. Hydro-RP Mercury 20 mm .times. 4
mm Flow rate: 1.0 ml/min Gradient: A: Water/0.1% formic acid B:
Acetonitrile/0.1% formic acid Time A % B % 0.00 90 10 2.50 30 70
3.00 5 95 4.50 5 95
[0075] UV spectra were recorded at 210 nm with a sampling rate of
1.0 spectra/second. Mass spectra were obtained using positive and
negative electrospray ionization over the range m/z 100 to 700. The
scan rate was 1.0 scan (m/z 100 to 700) per second.
Synthesis of Compounds
[0076] First of all general methods will be presented for the
synthesis of basic building blocks. In subsequent reactions these
basic building blocks can be functionalized via common methods of
organic syntheses to obtain the desired target compounds.
General Method 1A:
##STR00020##
[0078] This scheme illustrates the synthesis of the first
precursor, which ist the starting compound for the subsequent ring
closure reaction to form various hydronaphthalen derivatives.
[0079] To a solution of the cyclohexane-1,3-dione in water the
enone is added. Some ethanol is added to enhance the solubility and
the developing suspension is stirred for 7 days at room temperature
(after 6 days the white solid is completely dissolved). The
solution is mixed with toluene and the aqueous phase is extracted
with dichloromethane. The combined organic phases are washed with
saturated NaCl solution and dried over MgSO.sub.4. The solvent is
removed under reduced pressure and the crude product is purified
via column chromatography.
[0080] Alternatively, if the solubility capability of water is not
sufficient, the following general method can be used. To a solution
of the cyclohexane-1,3-dione, a 2.5 M solution of Triton B
(benzyltrimethylammoniumhydroxide) in methanol the enone dissolved
in methanol is added. The suspension is heated at gently elevated
temperature for 5 h and stirred afterwards at room temperature over
night. The solvent is removed under reduced pressure, toluene is
added, the phases are separated and the organic phase is extracted
with dichloromethane. The combined organic phases are washed with
saturated NaCl solution and dried over MgSO.sub.4. The solvent is
removed under reduced pressure and the crude product is purified
via column chromatography.
General Method 1B:
##STR00021##
[0082] This scheme illustrates the above-mentioned ring closure
reaction of the obtained compound according to the General Method
1A.
[0083] To a solution of said cyclohexane-1,3-dione in benzene
pyrrolidine is added and the suspension is heated under reflux by
means of a water separator for the azeotropic removing of the
water. Afterwards the benzene and excess pyrrolidine are removed
under reduced pressure. The obtained solid is dissolved in
dichloromethane and water. The phases are separated and the aqueous
phase is extracted with dichloromethane. The combined organic
phases are primary washed with saturated NH.sub.4Cl solution, then
with saturated NaHCO.sub.3 solution and finally with saturated NaCl
solution. It is dried over MgSO.sub.4, the solvent is removed under
reduced pressure and the crude product is purified via column
chromatography.
[0084] This ring closure reaction can be also carried out in a
stereoselective manner.
General Method 1C:
##STR00022##
[0086] This scheme illustrates the above-mentioned ring closure
reaction of the obtained compound according to General Method 1A
with controlled stereoselectivity.
[0087] To a solution of said cyclohexane-1,3-dione in DMF
L-phenylalanine and D-camphorsulfonic acid are added. The solution
is stirred over night at room temperature and afterwards the
temperature is increased every 24 h in each case by 10.degree. C.
until the final value of 70.degree. C. The solution is cooled to
0.degree. C. and mixed with a saturated NaHCO.sub.3 solution. After
some stirring it is extracted with diethylether. The combined
organic phases are washed with saturated NaCl solution and dried
over MgSO.sub.4. The solvent is removed under reduced pressure and
the crude product is purified via column chromatography.
[0088] This synthesis step takes place in all cases, which will be
described more detailed in the Examples 1 to 5 below.
[0089] As next the conversion of the carbonyl group an the position
5 of the hydronaphthalen into a hydroxy group takes place. Via the
obtained OH group the functionalization capability of these
compounds is achieved.
General Method 1D:
##STR00023##
[0091] This scheme illustrates the conversion of the carbonyl group
an the position 5.
[0092] To a solution of the desired compound in absolute ethanol a
solution of sodium borohydride in ethanol is added dropwise at
0.degree. C. within about 3 h. After some stirring the solution is
admixed with pure acetic acid dropwise, until no gas evolution is
observable. It is mixed with toluene and the solvent is removed
under vacuum. The residue is taken up in chloroform, washed with
saturated NaCl solution and dried over MgSO.sub.4. The solvent is
removed under reduced pressure and the crude product is purified
via column chromatography.
[0093] In the following Examples 1 to 5 according to the General
Method 1a detailed synthesis description is given. The compounds
synthesized are obtained via the stereoselective way.
Example 1
Synthesis of
(4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-o-
ne
##STR00024##
[0094] Synthesis of
2-methyl-2-(3-oxopentyl)cyclohexane-1,3-dione
[0095] To a solution of 37.5 g (298 mmol)
2-methylcyclohexane-1,3-dione in 75 ml of water 50.0 ml (512 mmol)
of pent-1-en-3-one is added. 2.5 ml of ethanol is added to enhance
the solubility and the developing suspension is stirred for 7 days
at room temperature (after 6 days the white solid is completely
dissolved). The solution is mixed with 300 ml of toluene and the
aqueous phase is extracted three times each with 300 ml of
dichloromethane. The combined organic phases are washed with
saturated NaCl solution and dried over MgSO.sub.4. The solvent is
removed under reduced pressure and the crude product is purified
via column chromatography (colorless oil).
[0096] Yield: 53.7 g, 256 mmol, 86%
[0097] R.sub.f-value: 0.16 (cyclohexane/ethylacetate 3:1 v/v)
[0098] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.02 (t, J=7.4
Hz, 3H), 1.24 (s, 3H), 1.98-2.10 (m, 2H), 2.2-2.58 (m, 10H).
[0099] GCMS, m/z (rel int. %): 210 (49) [M.sup.+], 192 (18), 181
(21), 153 (15), 139 (82), 111 (100), 97 (45), 69 (43), 57 (64).
Synthesis of
(S)-3,4,8,8a-tetrahydro-5,8a-dimethylnaphthalen-1,6(2H,7H)-dione
[0100] To a solution of 49.0 g (233 mmol)
2-methyl-2-(3-oxopentyl)cyclohexane-1,3-dione in 600 ml of DMF,
37.0 g (224 mmol) L-phenylalanine and 27.0 g (166 mmol)
D-camphorsulfonic acid are added. The solution is stirred over
night at room temperature and afterwards the temperature is
increased every 24 h in each case by 10.degree. C. until the final
value of 70.degree. C. The solution is cooled to 0.degree. C. and
mixed with 600 ml of a saturated NaHCO.sub.3 solution. After 30 min
of stirring it is extracted each time with 400 ml of diethylether.
The combined organic phases are washed with saturated NaCl solution
and dried over MgSO.sub.4. The solvent is removed under reduced
pressure and the crude product is purified via column
chromatography (white solid).
[0101] Mp.: 46.degree. C.
[0102] Yield: 32.0 g, 166.7 mmol, 71%
[0103] R.sub.f-value: 0.24 (cyclohexane/ethylacetate 3:1 v/v)
[0104] [.alpha.].sub.D.sup.20=+136.degree. (c=1.00, CHCl.sub.3)
[0105] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.41 (s, 3H),
1.80 (s, 3H), 2.02-2.21 (m, 4H), 2.38-2.59 (m, 4H), 2.81-2.94 (m,
1H).
[0106] GCMS, m/z (rel int. %): 192 (34) [M.sup.+], 177 (38), 149
(57), 136 (100), 121 (41), 107 (74), 93 (82), 79 (49), 55 (31), 39
(23).
Synthesis of
(4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-o-
ne
[0107] To a solution of 32.0 g (166.7 mmol)
(S)-3,4,8,8a-tetrahydro-5,8a-dimethylnaphthalen-1,6(2H,7H)-dione in
250 ml of absolute ethanol a solution of 1.68 g (44.4 mmol) sodium
borohydride in 70 ml of ethanol is added dropwise at 0.degree. C.
within 3 h. After 30 min of stirring the solution is admixed with
pure acetic acid dropwise, until no gas evolution is observable. It
is mixed with 50 ml of toluene and the solvent is removed under
vacuum. The residue is taken up in 500 ml of chloroform, washed
with saturated NaCl solution and dried over MgSO.sub.4. The solvent
is removed under reduced pressure and the crude product is purified
via column chromatography (colorless oil).
[0108] Yield: 25.2 g, 129.9 mmol, 78%
[0109] R.sub.f-value: 0.12 (cyclohexane/ethylacetate 3:1 v/v)
[0110] [.alpha.].sub.D.sup.20=+161.degree. (c=1.00, CHCl.sub.3)
[0111] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.11 (s, 3H),
1.21-1.35 (m, 1H), 1.69 (s, 3H), 1.58-1.92 (m, 4H), 1.94-2.10 (m,
2H), 2.30-2.39 (m, 2H), 2.55-2.65 (m, 1H), 3.34 (dd, J=4.5, 7.2 Hz,
1H), 3.60 (brs, 1H).
[0112] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 11.5, 16.0,
23.1, 27.3, 30.1, 33.6, 42.2, 78.3, 129.9, 161.8, 199.6.
[0113] GCMS, m/z (rel int. %): 194 (81) [M.sup.+], 179 (7), 151
(12), 138 (100), 123 (41), 110 (34), 91 (27), 77 (19), 67 (9), 55
(11) 41 (11).
Example 2
Synthesis of
(4S,4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H-
)-one
##STR00025##
[0114] Synthesis of
(8S,8aS)-3,4,8,8a-tetrahydro-8,8a-dimethylnaphthalen-1,6(2H,7H)-dione
[0115] To a solution of 10.0 g (80.1 mmol)
2-methylcyclohexane-1,3-dione in 75 ml of water 7.4 g (88.2 mmol)
of trans-pentene-2-one is added. 1.5 ml of ethanol is added to
enhance the solubility and the developing suspension is stirred for
7 days at room temperature (after 6 days the white solid is
completely dissolved). The solution is mixed with 200 ml of toluene
and the aqueous phase is extracted three times each with 200 ml of
dichloromethane. The combined organic phases are washed with
saturated NaCl solution and dried over MgSO.sub.4. The solvent is
removed under reduced pressure.
[0116] The residue is admixed with 300 ml of DMF, 18.5 g (112 mmol)
L-phenylalanine and 13.5 g (83.2 mmol) D-camphorsulfonic acid are
added. The solution is stirred over night at room temperature and
afterwards the temperature is increased every 24 h in each case by
10.degree. C. until the final value of 70.degree. C. The solution
is cooled to 0.degree. C. and mixed with 300 ml of a saturated
NaHCO.sub.3 solution. After 30 min of stirring it is extracted each
time with 250 ml of diethylether. The combined organic phases are
washed with saturated NaCl solution and dried over MgSO.sub.4. The
solvent is removed under reduced pressure and the crude product is
purified via column chromatography (white solid).
[0117] Mp.: 58.degree. C.
[0118] Yield: 9.49 g, 48.9 mmol, 61%
[0119] R.sub.f-value: 0.22 (cyclohexane/ethylacetate 3:1 v/v)
[0120] [.alpha.].sub.D.sup.20=+72.degree. (c=1.00, CHCl.sub.3)
[0121] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.78 (d, J=6.8
Hz, 3H), 1.36 (s, 3H), 1.52-1.65 (m, 1H), 1.94-2.03 (m, 1H),
2.09-2.15 (m, 2H), 2.31-2.38 (m, 1H), 2.43-2.67 (m, 4H), 5.85 (s,
1H).
[0122] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 16.8, 20.8,
26.2, 32.0, 35.8, 39.0, 41.5, 54.6, 124.8, 164.2, 197.9, 211.8.
[0123] GCMS, m/z (rel int. %): 192 (15) [M.sup.+], 174 (17), 150
(22), 135 (100), 122 (11), 107 (13), 94 (16), 79 (16), 55 (13), 39
(11).
[0124] HRMS (FAB): calc. for C.sub.12H.sub.16O.sub.2: 192.1150,
found: 193.1221 [M+H].sup.+.
Synthesis of
(4S,4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4,4a-dimethylnaphthalen-2(3H-
)-one
[0125] To a solution of 15.9 g (82.8 mmol)
(8S,8aS)-3,4,8,8a-tetrahydro-8,8a-dimethylnaphthalen-1,6(2H,7H)-dione
in 150 ml of absolute ethanol a solution of 776 mg (20.5 mmol)
sodium borohydride in 30 ml of ethanol is added dropwise at
0.degree. C. within 3 h. After 30 min of stirring the solution is
admixed with pure acetic acid dropwise, until no gas evolution is
observable. It is mixed with 20 ml of toluene and the solvent is
removed under vacuum. The residue is taken up in 300 ml of
chloroform, washed with saturated NaCl solution and dried over
MgSO.sub.4. The solvent is removed under reduced pressure and the
crude product is purified via column chromatography (colorless
oil).
[0126] Yield: 12.7 g, 65.4 mmol, 79%
[0127] R.sub.f-value: 0.12 (cyclohexane/ethylacetate 3:1 v/v)
[0128] [.alpha.].sub.D.sup.20=+880 (c=1.00, CHCl.sub.3)
[0129] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.79 (d, J=7.0
Hz, 3H), 1.26 (s, 3H), 1.20-1.40 (m, 1H), 1.40-1.59 (m, 1H),
1.98-2.04 (m, 2H), 2.11-2.18 (m, 1H), 2.43-2.67 (m, 6H), 6.07 (s,
1H).
[0130] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 17.6, 18.6,
26.0, 31.6, 36.3, 37.9, 42.3, 47.6, 82.8, 127.8, 177.1, 197.9.
[0131] GCMS, m/z (rel int. %): 194 (31) [M.sup.+], 161 (100), 138
(54), 109 (26), 91 (31), 77 (18), 67 (11), 55 (10), 41 (13).
[0132] HRMS (FAB): calc. for C.sub.12H.sub.18O.sub.2: 194.1307,
found: 195.1392 [M+H].sup.+.
Example 3
Synthesis of
(4aR,5R)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one
##STR00026##
[0133] Synthesis of
(S)-3,4,8,8a-tetrahydro-8a-methylnaphthalen-1,6(2H,7H)-dione
[0134] To a solution of 12.6 g (100 mmol)
2-methylcyclohexane-1,3-dione, 4.4 ml (11.0 mmol) of a 2.5 M
solution of Triton B (benzyltrimethylammoniumhydroxide) in methanol
14.6 ml (10.5 g, 150 mmol) of but-3-en-2-one is added in 60 ml of
methanol. The suspension is heated at 60.degree. C. for 5 h and
stirred afterwards at room temperature over night. The solvent is
removed under reduced pressure and the crude product is purified
via column chromatography.
[0135] It is admixed with 300 ml of DMF, 23.3 g (141 mmol)
L-phenylalanine and 17.0 g (105 mmol) D-camphorsulfonic acid are
added. The solution is stirred over night at room temperature and
afterwards the temperature is increased every 24 h in each case by
10.degree. C. until the final value of 70.degree. C. The solution
is cooled to 0.degree. C. and mixed with 300 ml of a saturated
NaHCO.sub.3 solution. After 30 min of stirring it is extracted each
time with 250 ml of diethylether. The combined organic phases are
washed with saturated NaCl solution and dried over MgSO.sub.4. The
solvent is removed under reduced pressure and the crude product is
purified via column chromatography (colorless oil).
[0136] Yield: 12.7 g, 65.4 mmol, 60%
[0137] R.sub.f-value: 0.27 (cyclohexane/ethylacetate 3:1 v/v)
[0138] [.alpha.].sub.D.sup.20=+103.degree. (c=1.09, CHCl.sub.3)
[0139] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.42 (s, 3H),
1.61-1.78 (m, 1H), 2.03-2.20 (m, 3H), 2.36-2.53 (m, 4H), 2.66-2.78
(m, 2H), 5.84 (s, 1H).
[0140] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 23.0, 23.4,
29.7, 31.8, 33.7, 37.7, 50.6, 125.7, 165.6, 198.0, 210.7.
[0141] GCMS, m/z (rel int. %): 178 (29) [M.sup.+], 160 (49), 150
(16), 136 (41), 121 (100), 108 (76), 93 (83), 79 (91), 55 (34), 39
(27).
[0142] HRMS (FAB): calc. for C.sub.11H.sub.14O.sub.2: 178.0994,
found: 179.1085 [M+H].sup.+.
Synthesis of
(4aR,5R)-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methylnaphthalen-2(3H)-one
[0143] To a solution of 17.0 g (95.5 mmol)
(S)-3,4,8,8a-tetrahydro-8a-methylnaphthalen-1,6(2H,7H)-dione in 150
ml of absolute ethanol a solution of 946 mg (25.0 mmol) sodium
borohydride in 30 ml of ethanol is added dropwise at 0.degree. C.
within 3 h. After 30 min of stirring the solution is admixed with
pure acetic acid dropwise, until no gas evolution is observable. It
is mixed with 20 ml of toluene and the solvent is removed under
vacuum. The residue is taken up in 300 ml of chloroform, washed
with saturated NaCl solution and dried over MgSO.sub.4. The solvent
is removed under reduced pressure and the crude product is purified
via column chromatography (colorless oil).
[0144] Yield: 13.9 g, 77.4 mmol, 81%
[0145] R.sub.f-value: 0.12 (cyclohexane/ethylacetate 3:1 v/v)
[0146] [.alpha.].sub.D.sup.20=+78.degree. (c=1.00, CHCl.sub.3)
[0147] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.17 (s, 3H),
1.22-1.53 (m, 6H), 1.80-2.78 (m, 5H), 3.31 (t, J=6.4 Hz, 1H), 5.71
(s, 1H).
[0148] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 14.3, 15.5,
21.2, 27.4, 30.3, 32.3, 33.8, 41.7, 60.6, 125.4, 171.6, 200.2.
[0149] GCMS, m/z (rel int. %): 180 (44) [M.sup.+], 162 (10), 152
(12), 137 (16), 124 (100), 109 (69), 91 (31), 79 (35), 67 (23), 55
(28), 43 (35).
[0150] HRMS (FAB): calc. for C.sub.11H.sub.16O.sub.2: 180.1150,
found: 181.1217 [M+H].sup.+.
Example 4
Synthesis of
(4aR,5S)-4a-benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(-
3H)-one
##STR00027##
[0151] Synthesis of
2-benzyl-2-(3-oxopentyl)cyclohexane-1,3-dione
[0152] To a solution of 20.2 g (100 mmol)
2-benzylcyclohexane-1,3-dione, 4.4 ml (11.0 mmol) of a 2.5 M
solution of Triton B (benzyltrimethylammoniumhydroxide) in methanol
12.6 ml (12.6 g, 150 mmol) of pent-1-ene-3-one is added in 60 ml of
methanol. The suspension is heated at 60.degree. C. for 5 h and
stirred afterwards at room temperature over night. The solvent is
removed under reduced pressure, 400 ml of toluene is added, the
phases are separated and the organic phase is extracted each time
with 300 ml of dichloromethane. The combined organic phases are
washed with saturated NaCl solution and dried over MgSO.sub.4. The
solvent is removed under reduced pressure and the crude product is
purified via column chromatography (colorless oil).
[0153] Yield: 22.9 g, 80.1 mmol, 80%
[0154] R.sub.f-value: 0.21 (cyclohexane/ethylacetate 3:1 v/v)
[0155] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.99 (t, J=7.0
Hz, 3H), 1.93-2.03 (m, 2H), 2.11-2.64 (m, 10H), 3.66 (s, 2H),
7.17-7.37 (m, 5H).
[0156] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 7.9, 16.1,
21.4, 35.9, 36.9 (2C), 37.1, 38.5, 70.7, 127.2, 128.1 (2C), 128.7
(2C), 135.2, 200.0, 210.0, 210.4.
[0157] GCMS, m/z (rel int. %): 286 (32) [M.sup.+], 258 (12), 202
(13), 187 (31), 173 (56), 158 (42), 115 (27), 91 (100), 57 (21), 42
(10).
[0158] HRMS (FAB): calc. for C.sub.18H.sub.22O.sub.3: 286.1569,
found: 287.1655 [M+H].sup.+.
Synthesis of
(R)-8a-benzyl-3,4,8,8a-tetrahydro-5-methylnaphthalen-1,6(2H,7H)-dione
[0159] To a solution of 20.0 g (69.9 mmol)
2-benzyl-2-(3-oxopentyl)cyclohexane-1,3-dione in 400 ml of DMF,
11.1 g (66.9 mmol) L-phenylalanine and 8.1 g (49.8 mmol)
D-camphorsulfonic acid are added. The solution is stirred over
night at room temperature and afterwards the temperature is
increased every 24 h in each case by 10.degree. C. until the final
value of 70.degree. C. The solution is cooled to 0.degree. C. and
mixed with 500 ml of a saturated NaHCO.sub.3 solution. After 30 min
of stirring it is extracted each time with 300 ml of diethylether.
The combined organic phases are washed with saturated NaCl solution
and dried over MgSO.sub.4. The solvent is removed under reduced
pressure and the crude product is purified via column
chromatography (white solid).
[0160] Mp.: 67.degree. C.
[0161] Yield: 13.3 g, 49.6 mmol, 71%
[0162] R.sub.f-value: 0.12 (cyclohexane/ethylacetate 3:1 v/v)
[0163] [.alpha.].sub.V.sup.20=+78.degree. (c=1.00, CHCl.sub.3)
[0164] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.65-1.75 (m,
1H), 1.86 (s, 3H), 1.87-1.91 (m, 1H), 1.91-2.02 (m, 2H), 2.07-2.12
(m, 1H), 2.36-2.52 (m, 5H), 2.60-2.71 (m, 1H), 2.83-2.91 (m, 1H),
6.97-7.03 (m, 1H), 7.24-7.30 (m, 2H), 7.37-7.42 (m, 2H).
[0165] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 11.8, 21.5,
27.1, 29.3, 37.0, 38.9, 43.2, 56.1, 127.2, 128.7, 129.8 (4C),
141.2, 157.9, 197.7, 211.1.
[0166] GCMS, m/z (rel int. %): 268 (17) [M.sup.+], 176 (9), 141
(8), 115 (11), 91 (100), 77 (12), 65 (12).
[0167] HRMS (FAB): calc. for C.sub.18H.sub.20O.sub.2: 268.1463,
found: 269.1530 [M+H].sup.+.
Synthesis of
(4aR,5S)-4a-benzyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-1-methylnaphthalen-2(-
3H)
[0168] To a solution of 12.8 g (47.8 mmol)
(R)-8a-benzyl-3,4,8,8a-tetrahydro-5-methylnaphthalen-1,6(2H,7H)-dione
in 100 ml of absolute ethanol a solution of 473 mg (12.5 mmol)
sodium borohydride in 20 ml of ethanol is added dropwise at
0.degree. C. within 2.5 h. After 30 min of stirring the solution is
admixed with pure acetic acid dropwise, until no gas evolution is
observable. It is mixed with 20 ml of toluene and the solvent is
removed under vacuum. The residue is taken up in 300 ml of
chloroform, washed two times with saturated NaCl solution and dried
over MgSO.sub.4. The solvent is removed under reduced pressure and
the crude product is purified via column chromatography (colorless
oil).
[0169] Yield: 13.9 g, 77.4 mmol, 81%
[0170] R.sub.f-value: 0.10 (cyclohexane/ethylacetate 3:1 v/v)
[0171] [.alpha.].sub.D.sup.20=+72.degree. (c=1.01, CHCl.sub.3)
[0172] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.23-1.57 (m,
6H), 1.82 (s, 3H), 1.90-2.09 (m, 2H), 2.26-2.51 (m, 2H), 2.74-2.87
(m, 1H), 2.95-3.02 (m, 1H), 3.20-3.26 (m, 1H), 7.04-7.12 (m, 1H),
716-7.20 (m, 2H), 7.35-7.40 (m, 2H).
[0173] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 11.7, 23.8,
27.7, 30.9, 31.1, 33.7, 36.7, 46.8, 80.1, 126.9, 129.9 (4C), 132.7,
138.6, 157.6, 199.2.
[0174] GCMS, m/z (rel int. %): 270 (41) [M.sup.+], 178 (35), 161
(100), 137 (16), 105 (22), 91 (76), 79 (25), 67 (13), 55 (18), 43
(25).
[0175] HRMS (FAB): calc. for C.sub.18H.sub.22O.sub.2: 270.1620,
found: 271.1712 [M+H].sup.+.
Example 5
Synthesis of
(4S,4aS,5S)-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen--
2(3H)-one
##STR00028##
[0176] Synthesis of 2-allylcyclohexane-1,3-dione
[0177] To a solution of 92.6 g (826 mmol) cyclohexane-1,3-dione in
100 ml of water and 200 ml (500 mmol) of a 2.5 M solution of Triton
B (benzyltrimethylammoniumhydroxide) in methanol 69.9 ml (100 g,
826 mmol) of 3-bromoprop-1-en is added in 60 ml of methanol. The
suspension is stirred at room temperature over night. The solvent
is removed under reduced pressure, 400 ml of toluene is added, the
phases are separated and the organic phase is extracted each time
with 300 ml of dichloromethane. The combined organic phases are
washed with saturated NaCl solution and dried over MgSO.sub.4. The
solvent is removed under reduced pressure and the crude product is
purified via column chromatography (colorless oil).
[0178] Yield: 82.9 g, 545 mmol, 66%
[0179] R.sub.f-value: 0.48 (cyclohexane/ethylacetate 3:1 v/v)
[0180] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.70-2.80 (m,
8H), 3.19 (t, J=6.9 Hz, 1H), 5.01-5.13 (m, 2H), 5.57-5.68 (m,
1H).
[0181] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 15.2, 29.0,
40.9 (2C), 67.1, 116.4, 134.4, 208.3 (2C).
[0182] GCMS, m/z (rel int. %): 152 (41) [M.sup.+], 137 (61), 124
(49), 109 (14), 96 (100), 81 (34), 67 (21), 55 (44), 39 (23).
[0183] HRMS (FAB): calc. for C.sub.9H.sub.12O.sub.2: 152.0837,
found: 153.0912 [M+H].sup.+.
Synthesis of
(8S,8aS)-8a-allyl-3,4,8,8a-tetrahydro-8-methylnaphthalen-1,6(2H,7H)-dione
[0184] To a solution of 13.4 g (88.1 mmol)
2-allylcyclohexane-1,3-dione in 75 ml of water 8.2 g (97.2 mmol) of
pent-3-ene-2-one is added. 1.5 ml of ethanol is added to enhance
the solubility and the developing suspension is stirred for 7 days
at room temperature (after 6 days the white solid is completely
dissolved). The solution is mixed with 200 ml of toluene and the
aqueous phase is extracted three times each with 200 ml of
dichloromethane. The combined organic phases are washed with
saturated NaCl solution and dried over MgSO.sub.4. The solvent is
removed under reduced pressure and the crude product is purified
via column chromatography.
[0185] Afterwards it is admixed with 400 ml of DMF, 24.8 g (150
mmol) L-phenylalanine and 18.1 g (111 mmol) D-camphorsulfonic acid
are added. The solution is stirred over night at room temperature
and afterwards the temperature is increased every 24 h in each case
by 10.degree. C. until the final value of 70.degree. C. The
solution is cooled to 0.degree. C. and mixed with 400 ml of a
saturated NaHCO.sub.3 solution. After 30 min of stirring it is
extracted each time with 300 ml of diethylether. The combined
organic phases are washed with saturated NaCl solution and dried
over MgSO.sub.4. The solvent is removed under reduced pressure and
the crude product is purified via column chromatography (white
solid).
[0186] Mp.: 52.degree. C.
[0187] Yield: 10.4 g, 47.7 mmol, 54%
[0188] R.sub.f-value: 0.37 (cyclohexane/ethylacetate 3:1 v/v)
[0189] [.alpha.].sub.D.sup.20=+54.degree. (c=1.00, CHCl.sub.3)
[0190] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.84 (d, J=7.6
Hz, 3H), 1.54-1.70 (m, 1H), 1.91-2.74 (m, 11H), 5.01-5.13 (m, 2H),
5.58-5.71 (m, 1H).
[0191] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 17.0, 21.1,
33.2, 33.7, 40.3, 41.2, 43.8, 58.6, 119.3, 125.3, 132.7, 163.8,
197.9, 210.2.
[0192] GCMS, m/z (rel int. %): 218 (52) [M.sup.+], 203 (31), 190
(10), 175 (24), 161 (22), 149 (100), 135 (26), 119 (14), 105 (41),
91 (49), 77 (36), 55 (27), 41 (23).
[0193] HRMS (FAB): calc. for C.sub.14H.sub.18O.sub.2: 218.1307,
found: 219.1391 [M+H].sup.+.
Synthesis of
(4S,4aS,5S)-4a-allyl-4,4a,5,6,7,8-hexahydro-5-hydroxy-4-methylnaphthalen--
2(3H)-one
[0194] To a solution of 9.9 g (45.5 mmol)
(8S,8aS)-8a-allyl-3,4,8,8a-tetrahydro-8-methylnaphthalen-1,6(2H,7H)-dione
in 100 ml of absolute ethanol a solution of 483 mg (12.5 mmol)
sodium borohydride in 20 ml of ethanol is added dropwise at
0.degree. C. within 3 h. After 30 min of stirring the solution is
admixed with pure acetic acid dropwise, until no gas evolution is
observable. It is mixed with 20 ml of toluene and the solvent is
removed under vacuum. The residue is taken up in 300 ml of
chloroform, washed with saturated NaCl solution and dried over
MgSO.sub.4. The solvent is removed under reduced pressure and the
crude product is purified via column chromatography (colorless
oil).
[0195] Yield: 8.0 g, 36.3 mmol, 80%
[0196] R.sub.f-value: 0.14 (cyclohexane/ethylacetate 3:1 v/v)
[0197] [.alpha.].sub.D.sup.20=+660 (c=1.03, CHCl.sub.3)
[0198] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.85 (d, J=8.0
Hz, 3H), 1.28-2.74 (m, 11H), 3.21-3.26 (m, 1H), 5.04-5.17 (m, 2H),
5.58-5.70 (m, 2H).
[0199] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 16.9, 23.6,
28.5, 32.6, 35.4, 36.1, 44.7, 51.8, 79.5, 115.9, 123.8, 139.1,
170.0, 199.1.
[0200] GCMS, m/z (rel int. %): 220 (13) [M.sup.+], 202 (11), 179
(22), 161 (39), 137 (61), 119 (100), 105 (29), 91 (31), 77 (28), 65
(15), 55 (14), 41 (23).
[0201] HRMS (FAB): calc. for C.sub.14H.sub.20O.sub.2: 220.1463,
found: 221.1551 [M+H].sup.+.
General Method 2:
##STR00029##
[0203] This scheme illustrates the hydrogenation reaction of the
above described compounds. Said reaction can also be applied to
compounds having other substituents than a hydroxy group in
position 5. Normally, this reaction is enantioselective or
diastereoselective, respectively.
[0204] To a solution of the compound to be hydrogenated in pyridine
Pd/C are added. The obtained suspension is well stirred over night
under a hydrogene atmosphere. Dichloromethane is added and the
suspension is filtered over celite. The filtrate is primary washed
with saturated NH.sub.4Cl solution, then with saturated NaCl
solution. The solvent is removed under reduced pressure and the
crude product is dissolved in methanol. A solution of sodium
mathanoate in methanol is added and the solution is stirred under
reflux. After cooling to room temperature dichloromethane and water
is added. The phases are separated and the aqueous phase is
extracted with dichloromethane. The combined organic phases are
washed with saturated NH.sub.4Cl solution, then with saturated NaCl
solution and dried over MgSO.sub.4. The solvent is removed under
reduced pressure and the crude product is purified via column
chromatography.
Example 6
Synthesis of
(1S,4aS,5S,8aR)-octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one
##STR00030##
[0206] To a solution of 18.0 g (92.8 mmol) of
(4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-o-
ne in 100 ml of pyridine 0.4 g Pd/C are added. The obtained
suspension is well stirred over night under a hydrogene atmosphere.
250 ml dichloromethane are added and the suspension is filtered
over celite. The filtrate is primary washed with saturated
NH.sub.4Cl solution, then with saturated NaCl solution. The solvent
is removed under reduced pressure and the crude product is
dissolved in 150 ml of methanol. 23.0 ml (124 mmol) of a 5.4 M
solution of sodium mathanoate in methanol is added and the solution
is stirred under reflux for 2 h. After cooling to room temperature
300 ml of dichloromethane and 300 ml of water is added. The phases
are separated and the aqueous phase is extracted three times with
dichloromethane. The combined organic phases are washed with
saturated NH.sub.4Cl solution, then with saturated NaCl solution
and dried over MgSO.sub.4. The solvent is removed under reduced
pressure and the crude product is purified via column
chromatography (colorless oil).
[0207] Yield: 11.2 g, 57.1 mmol, 62%
[0208] R.sub.f-value: 0.15 (cyclohexane/ethylacetate 3:1 v/v)
[0209] [.alpha.].sub.D.sup.20=-98.degree. (c=1.00, CHCl.sub.3)
[0210] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.96 (d, J=5.9
Hz, 3H), 1.07 (s, 3H), 1.17-1.85 (m, 9H), 2.19-2.55 (m, 4H), 3.22
(dd, J=4.5, 7.0 Hz, 1H).
[0211] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 10.3, 11.7,
24.3, 25.1, 30.0, 34.0, 37.7, 39.2, 44.8, 50.8, 79.0, 213.0.
[0212] GCMS, m/z (rel int. %): 196 (26) [M.sup.+], 181 (21), 163
(17), 145 (10), 135 (51), 111 (100), 107 (32), 93 (12), 79 (9), 67
(11), 55 (10), 41 (9).
[0213] HRMS (FAB): calc. for C.sub.12H.sub.20O.sub.2: 196.1463,
found: 197.1558 [M+H].sup.+.
General Method 3:
##STR00031##
[0215] This scheme illustrates the hydrogenation reaction of the
above described compounds and the additional conversion of the
carbonyl group in position 2 to a hydroxyl group.
[0216] To a solution of the compound in dichloromethane
2-ethyl-2-methyl-1,3-dioxolan as well as catalytic amounts of
ethyleneglycol and p-toluenesulfonic acid are added. The solution
first stirred for 2 days at room temperature, then admixed with
some ml of triethylamine and dichloromethane. The organic phase is
washed with saturated NaCl solution and dried over MgSO.sub.4. The
solvent is removed under reduced pressure and the crude product is
purified via column chromatography.
[0217] To a solution of the dioxolan protected compound in pyridine
Pd/C are added. The obtained suspension is well stirred over night
under a hydrogene atmosphere of 12 bar at elevated temperature for
3 days. Dichloromethane is added and the suspension is filtered
over celite. The filtrate is primary washed with saturated
NH.sub.4Cl solution, then with saturated NaCl solution, finally it
is dried over MgSO.sub.4. The solvent is removed under reduced
pressure and the crude product is dissolved in methanol. A 5.4 M
solution of sodium mathanoate in methanol is added and the solution
is stirred under reflux for 2 h. After cooling to room temperature
dichloromethane and an equal amount of water is added. The phases
are separated and the aqueous phase is extracted with
dichloromethane. The combined organic phases are washed with
saturated NH.sub.4Cl solution, then with saturated NaCl solution
and dried over MgSO.sub.4. The solvent is removed under reduced
pressure and the crude product is purified via column
chromatography.
[0218] To a solution of the dioxolan protected hydrogenated
compound in absolute diethylether a 1.0 M solution of
diisobutylaluminiumhydride in toluene is added at -78.degree. C. It
is stirred at -78.degree. C. for 1 h and then it is let to warm to
room temperature. The solution is stirred at room temperature for
some min, again cooled to -78.degree. C. and quenched with
saturated NH.sub.4Cl solution. The solution is warmed to room
temperature, the phases are separated and the aqueous phase is
extracted with diethylether. The combined organic phases are washed
with saturated NaCl solution and dried over MgSO.sub.4. The solvent
is removed under reduced pressure and the crude product is purified
via column chromatography.
[0219] To remove the dioxolan protection group to a solution of the
obtained compound in a 1:1 (v/v) mixture of acetone and water
2-hydroxy-pyridinium-(p-toluenesulfonate) is added and stirred at
elevated temperature for 2 h. After cooling down to room
temperature saturated NaHCO.sub.3 solution is added, the phases are
separated and the aqueous phase is extracted with dichloromethane.
The combined organic phases are washed with saturated NaCl solution
and dried over MgSO.sub.4. The solvent is removed under reduced
pressure and the crude product is purified via column
chromatography.
Example 7
Synthesis of
(5S,8aS)-octahydro-6-hydroxy-5,8a-dimethylnaphthalen-1(2H)-one
##STR00032##
[0220] Synthesis of
(S)-4,4a,5,6,7,8-hexahydro-5-(1,3-dioxolan)-1,4a-dimethylnaphthalen-2(3H)-
-one
[0221] To a solution of 10.5 g (53.8 mmol)
(S)-3,4,8,8a-tetrahydro-5,8a-dimethylnaphthalen-1,6(2H,7H)-dione in
100 ml of dichloromethane 100 ml of 2-ethyl-2-methyl-1,3-dioxolan
as well as catalytic amounts of ethyleneglycol and
p-toluenesulfonic acid are added. The solution is stirred for 2
days at room temperature, then admixed with 4 ml of triethylamine
and 400 ml of dichloromethane. The organic phase is washed with
saturated NaCl solution and dried over MgSO.sub.4. The solvent is
removed under reduced pressure and the crude product is purified
via column chromatography (colorless oil).
[0222] Yield: 11.0 g, 48.4 mmol, 90%
[0223] R.sub.f-value: 0.33 (cyclohexane/ethylacetate 3:1 v/v)
[0224] [.alpha.].sub.D.sup.20=+125.degree. (c=1.39, CHCl.sub.3)
[0225] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.34 (s, 3H),
1.57-1.72 (m, 5H), 1.76 (d, J=1.2 Hz, 3H), 2.02-2.25 (m, 2H),
2.32-2.50 (m, 2H), 2.67-2.76 (m, 1H), 3.87-4.00 (m, 4H).
[0226] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 11.5, 20.9,
21.4, 26.4, 26.5, 29.7, 33.7, 45.3, 65.0, 65.3, 112.8, 130.1,
156.0, 198.5.
[0227] GCMS, m/z (rel int. %): 236 (21) [M.sup.+], 180 (12), 149
(21), 121 (17), 107 (15), 99 (100), 91 (34), 77 (25), 55 (18), 41
(12).
[0228] HRMS (FAB): calc. for C.sub.14H.sub.20O.sub.3: 236.1412,
found: 237.1477 [M+H].sup.+.
Synthesis of
(1S,4aS)-octahydro-5-(1,3-dioxolan)-1,4a-dimethylnaphthalen-2(1H)-one
[0229] To a solution of 2.79 g (11.8 mmol) of
(S)-4,4a,5,6,7,8-hexahydro-5-(1,3-dioxolan)-1,4a-dimethylnaphthalen-2(3H)-
-one in 50 ml of pyridine 0.2 g Pd/C are added. The obtained
suspension is well stirred over night under a hydrogene atmosphere
of 12 bar at 65.degree. C. for 3 days. 250 ml dichloromethane are
added and the suspension is filtered over celite. The filtrate is
primary washed with saturated NH.sub.4Cl solution, then with
saturated NaCl solution, finally it is dried over MgSO.sub.4. The
solvent is removed under reduced pressure and the crude product is
dissolved in 20 ml of methanol. 2.3 ml (12.4 mmol) of a 5.4 M
solution of sodium mathanoate in methanol is added and the solution
is stirred under reflux for 2 h. After cooling to room temperature
200 ml of dichloromethane and 200 ml of water is added. The phases
are separated and the aqueous phase is extracted two times with
dichloromethane. The combined organic phases are washed with
saturated NH.sub.4Cl solution, then with saturated NaCl solution
and dried over MgSO.sub.4. The solvent is removed under reduced
pressure and the crude product is purified via column
chromatography (colorless oil).
[0230] Yield: 2.31 g, 9.7 mmol, 82%
[0231] R.sub.f-value: 0.31 (cyclohexane/ethylacetate 3:1 v/v)
[0232] [.alpha.].sub.D.sup.20=+83.degree. (c=1.09, CHCl.sub.3)
[0233] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.94 (d, J=6.6
Hz, 3H), 1.25 (s, 3H), 1.32-1.83 (m, 8H), 1.90-2.00 (m, 1H),
2.07-2.29 (m, 2H), 2.37-2.48 (m, 1H), 3.83-4.00 (m, 4H).
[0234] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 12.4, 17.5,
22.6, 22.8, 25.9, 29.8, 38.2, 43.1, 44.1, 49.8, 65.4 (2C), 112.6,
213.4.
[0235] GCMS, m/z (rel int. %): 238 (17) [M.sup.+], 209 (31), 138
(11), 112 (74), 99 (100), 86 (78), 67 (14), 55 (21), 41 (16).
[0236] HRMS (FAB): calc. for C.sub.14H.sub.22O.sub.3: 238.1569,
found: 239.1659 [M+H].sup.+.
Synthesis of
(1S,4aS)-decahydro-5-(1,3-dioxolan)-1,4a-dimethylnaphthalen-2-ol
[0237] To a solution of 3.41 g (14.3 mmol)
(1S,4aS)-octahydro-5-(1,3-dioxolan)-1,4a-dimethylnaphthalen-2(1H)-one
in 20 ml of absolute diethylether 14.5 ml (14.5 mmol) of a 1.0 M
solution of diisobutylaluminiumhydride in toluene is added at
-78.degree. C. It is stirred at -78.degree. C. for 1 h and then it
is let to warm to room temperature. The solution is stirred at room
temperature for 15 min, again cooled to -78.degree. C. and quenched
with 15 ml of saturated NH.sub.4Cl solution. The solution is warmed
to room temperature, the phases are separated and the aqueous phase
is extracted two times with diethylether. The combined organic
phases are washed with saturated NaCl solution and dried over
MgSO.sub.4. The solvent is removed under reduced pressure and the
crude product is purified via column chromatography (colorless
oil).
[0238] Yield: 3.05 g, 12.7 mmol, 89%
[0239] R.sub.f-value: 0.33 (cyclohexane/ethylacetate 3:1 v/v)
[0240] [.alpha.].sub.D.sup.20=+113.degree. (c=1.39, CHCl.sub.3)
[0241] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.92-1.00 (m,
3H), 1.12 (s, 3H), 1.24-1.83 (m, 12H), 2.31 (brs, 1H), 3.16 (m,
1H), 3.83-4.00 (m, 4H).
[0242] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 12.7, 16.8,
20.9, 22.8, 23.6, 29.8, 32.0, 44.2, 44.3, 44.8, 65.4 (2C), 80.0,
112.8.
[0243] GCMS, m/z (rel int. %): 240 (11) [M.sup.+], 222 (13), 195
(10), 178 (12), 160 (16), 145 (15), 125 (26), 113 (22), 99 (100),
86 (71), 67 (10), 55 (18), 41 (12).
[0244] HRMS (FAB): calc. for C.sub.14H.sub.24O.sub.3: 240.1725,
found: 241.1817 [M+H].sup.+.
Synthesis of
(5S,8aS)-octahydro-6-hydroxy-5,8a-dimethylnaphthalen-1(2H)-one
[0245] To a solution of 5.30 g (22.1 mmol)
(1S,4aS)-decahydro-5-(1,3-dioxolan)-1,4a-dimethylnaphthalen-2-ol in
100 ml of a 1:1 (v/v) mixture of acetone and water 15.0 g (56.1
mmol) of 2-hydroxy-pyridinium-(p-toluenesulfonate) are added and
stirred at 70.degree. C. for 2 h. After cooling down to room
temperature 400 ml of a saturated NaHCO.sub.3 solution are added,
the phases are separated and the aqueous phase is extracted three
times with 500 ml of dichloromethane. The combined organic phases
are washed with saturated NaCl solution and dried over MgSO.sub.4.
The solvent is removed under reduced pressure and the crude product
is purified via column chromatography (colorless oil).
[0246] Yield: 3.51 g, 18.1 mmol, 82%
[0247] R.sub.f-value: 0.33 (cyclohexane/ethylacetate 3:1 v/v)
[0248] [.alpha.].sub.D.sup.20=+125.degree. (c=1.39, CHCl.sub.3)
[0249] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.97 (d, J=6.4
Hz, 3H), 1.27 (s, 3H), 1.38-2.05 (m, 10H), 2.12-2.31 (m, 2H),
3.10-3.17 (m, 1H).
[0250] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 11.0, 21.4,
23.1, 27.2, 28.7, 35.6, 39.0, 45.2, 45.4, 55.2, 79.5, 214.3.
[0251] GCMS, m/z (rel int. %): 196 (32) [M.sup.+], 178 (81), 163
(31), 135 (100), 111 (75), 107 (71), 95 (62), 81 (66), 67 (69), 55
(73), 41 (78).
[0252] HRMS (FAB): calc. for C.sub.12H.sub.20O.sub.2: 196.1463,
found: 196.1481 [M].sup.+.
[0253] In the subsequent General Methods various syntheses of
organic chemistry will be described for solid phase reactions.
These comprise amongst others the aldol, Sonogashira, reductive
amination, amination of aryliodides, alkylation, Wittig, cleavage
of silyl protection groups, and the Heck reaction, which can be
also carried out in liquid phase. But it is stressed that these
reactions are not limited to solid phase syntheses.
[0254] First basic methods for the loading of the polymer substrate
as well as for the cleavage from the polymer substrate will be
described.
Functionalization of the Merrifield Resin with the THP Linker
[0255] To a solution of 21.9 g (192 mmol)
(3,4-dihydro-2H-pyran-2-yl)methanol in 150 ml of absolute THF 7.72
g (193 mmol) sodium hydride (60 percent in mass, in petroleum) are
added and the suspension is shaked at room temperature over night.
The solvent is removed under reduced pressure, afterwards 300 ml of
N,N-dimethylacetamide are added and the solution is shaked for 5
min at room temperature. Afterwards 25.0 g (42.5 mmol, load ratio:
1.7 mmol/g) of Merrifield resin is added slowly, such that no clots
are formed. The mixture is shaked for 2 days at room temperature
and the resin is washed three times each with methanol,
dichloromethane, dichloromethane:methanol=1:1 (v/v), methanol, and
dichloromethane. Finally the resin is dried under vacuum.
Determination of the Load Ratio
[0256] For determining the load ratio 300 mg of the dried resin are
mixed with 20 ml of dichloromethane and shaked for 15 min.
Afterwards 495 mg (2.55 mmol) of
(4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-o-
ne as well as 48 mg (0.255 mmol) p-toluenesulfonic acid monohydrate
are added and it is shaked over night. The solvent is filtered off
and the resin is washed three times each with dichloromethane,
dichloromethane:methanol=1:1 (v/v), methanol,
dichloromethane:methanol=1:1 (v/v), and dichloromethane. Finally
the resin is dried under vacuum. Afterwards 10 ml of a 10% solution
of trifluoroacetic acid in dichloromethane are added and it is
shaked for 10 min. The solvent is filtered off and the resin is
shaked again ten times with 10 ml of the trifluoroacetic acid
solution. 3 ml of toluene are added to the combined filtrates and
the solvent is removed under reduced pressure.
[0257] Yield: 64.6 mg, 0.33 mmol, 65%, load ratio: 1.10 mmol/g
[0258] [.alpha.].sub.D.sup.20=+1610 (c=1.06, CHCl.sub.3)
[0259] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.11 (s, 3H),
1.21-1.35 (m, 1H), 1.69 (s, 3H), 1.58-1.92 (m, 4H), 1.94-2.10 (m,
2H), 2.30-2.39 (m, 2H), 2.55-2.65 (m, 1H), 3.34 (dd, J=4.5, 7.2 Hz,
1H), 3.60 (brs, 1H).
Loading the Polymer Substrate (Resin):
[0260] 1.0 eq. of THP-functionalized Merrifield resin are shaked in
dichloromethane (15 ml/g) for 15 min. Afterwards 5 eq. of the
alcohol to be coupled as well as 0.5 eq. of p-toluolsulfonic acid
monohydrate are added, the mixture is shaked over night. The
solvent is filtered off and the resin is washed three times each
with dichloromethane, dichloromethane:methanol=1:1 (v/v), methanol,
dichloromethane:methanol=1:1 (v/v) and dichloromethane. Finally the
resin is dried under vacuum.
[0261] For determining the load ratio 30 mg of the dried resin are
mixed with 2 ml of dichloromethane and it is shaked for 15 min.
Afterwards 5 ml of a 10% solution of trifluoroacetic acid in
dichloromethane is added and it is shaked for 10 min. The solvent
is filtered off and the resin is shaked two times with 5 ml of the
trifluoroacetic acid solution. To the combined filtrates 3 ml of
toluene are added and the solvent is removed under reduced
pressure. Amount and purity of the cleaved alcohol represent the
load ration of the resin.
Cleavage from Polymer Substrate (Resin):
[0262] 30 mg of the dried resin are added with 2 ml dichloromethane
under argon and it is shaked for 15 min. Afterwards the solvent is
filtered off and 3 ml of a 10% solution of trifluoroacetic acid in
dichloromethane (v/v) is added and it is shaked for 10 min. The
solvent is filtered off and the resin is shaked two times with 3 ml
of the trifluoroacetic acid solution. To the combined filtrates 3
ml of toluene are added and the solvent is removed under reduced
pressure. The obtained product is dissolved in 100 .mu.l of
acetonitrile and purified over a HPLC column (flow rate: 27 ml/min;
CH.sub.3CN/H.sub.2O/TFA:10/90/0.1 (0 min), 30/70/0.1 (2 min), to
60/40/0.1 (15 min), to 80/20/0.1 (25 min), to 100/0/0.1 (26
min).
General Method 4:
##STR00033##
[0264] General method for the Wittig reaction at the solid
phase.
[0265] The Wittig reaction allows the synthesis of alkenes via the
reaction of aldehydes or ketones with ylides. The ylides are
generated in situ by deprotonation of a phosphonium salt with a
suitable base (e.g. NaH, NaOMe, NEt.sub.3).
[0266] The E/Z selectivity of the Wittig reaction depends
substantially from the stability of the used ylide. Stabilized
ylides lead predominantly to (E)-alkenes, whereas non stabilized
ylides lead to (Z)-alkenes.
[0267] 1 eq. of the polymer bound ketone is admixed with toluene (2
ml/g resin) and it is shaked for 15 min. Afterwards 10 eq. of the
corresponding triphenylphosphonium bromine and 8 eq. of
butyllithium in toluene are added at room temperature. The solution
is shaked for 15 min at room temperature and at 100.degree. C. over
night. The solvent is filtered off and the resin is washed three
times each with toluene, dichloromethane:toluene=1:1 (v/v),
dichloromethane:methanol=1:1 (v/v), methanol,
dichloromethane:methanol=1:1 (v/v) and dichloromethane. Afterwards
the resin is dried under vacuum.
Example 8
Synthesis of
(1S,6Z,8aS)-6-ethylidene-1,2,3,4,6,7,8,8a-octahydro-5,8a-dimethylnaphthal-
en-1-ol
##STR00034##
[0269] 50 mg (55 .mu.mol) of polymer bound
(4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-o-
ne are converted with 203 mg (0.55 mmol) of
ethyl-triphenylphosphoniumbromide and 0.28 ml (0.44 mmol) of a 1.6
M solution of butyllithium in toluene. The cleavage from the
polymer substrate is as described above (colorless oil).
[0270] Yield: 5.1 mg, 25 .mu.mol, 46%
[0271] [.alpha.].sub.D.sup.20=+46.degree. (c=1.07, CHCl.sub.3)
[0272] E/Z ratio: 1:2.1
[0273] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.20 (s, 3H),
1.11-2.07 (m, 13H), 1.59 (s, 3H), 3.10 (brs, 1H), 3.37-3.45 (m,
1H), 5.30-5.38 (m, 1H).
[0274] .sup.13C-NMR (100.6 MHz, CDCl.sub.3): .delta. 13.9, 14.7,
19.7, 24.9, 25.1, 28.6, 32.2, 40.4, 45.1, 86.7, 124.1, 135.9,
141.4, 152.3.
[0275] HRMS (FAB): calc. for C.sub.14H.sub.22O: 206.1671, found:
206.1678 [M].sup.+.
General Method 5:
##STR00035##
[0277] General method for the Leuckart-Wallach reaction at the
solid phase.
[0278] This conversion is an important possibility for the
synthesis of amines. Starting with a primary or secondary amine,
alkylated amines can be obtained from carbonyl compounds (aldehydes
or ketones) by means of formic acid as reducing agent. This
reductive carbonyl-amination leads to the same result as the
catalytic reductive amination of aldehydes and ketones, however
under substantially easier conditions (autoclave not necessary) and
with the advantage, that also compounds can be used, which normally
would contaminate the hydrogenation catalyst.
[0279] In this variant of the Leuckart-Wallach reaction sodium
cyanoborohydride is used instead of formic acid as reducing
agent.
[0280] 1 eq. of the dried resin is added with toluene (5 ml/g
resin), 1.6 eq. of titan(IV)-chloride in toluene and 3.8 eq. of the
corresponding amine under argon. Afterwards it is shaked over night
at 90.degree. C. The solvent is filtered off and the resin is
washed three times each with toluene, dichloromethane: methanol=1:1
(v/v), methanol, dichloromethane:methanol=1:1 (v/v), and
dichloromethane. Afterwards the resin is dried under vacuum and
admixed with THF (3 ml/g resin) and 1.5 eq. of sodium
cyanoborohydride. It is stirred at room temperature over night. The
solvent is filtered off and the resin is washed three times each
with THF, dichloromethane: methanol=1:1 (v/v), methanol,
dichloromethane:methanol=1:1 (v/v), and dichloromethane. Finally
the resin is dried under vacuum.
General Method 6:
##STR00036##
[0282] General method for the alkylation reaction at the solid
phase.
[0283] To 1 eq. of the resin, which was initially swelled two times
with dry THF for 15 min and washed, 5.0 eq. of potassium hydride in
THF (3 ml/mmol) are added at room temperature. It is shaked for 30
min at room temperature, 8 eq. of the corresponding bromide are
added and it is shaked for 1 h at room temperature as well as for 2
h at 50.degree. C. The solvent is filtered off and the resin is
washed three times each with THF, dichloromethane:THF=1:1 (v/v),
methanol, dichloromethane:methanol=1:1 (v/v), and dichloromethane.
Finally the resin is dried under vacuum.
Example 9
Synthesis of
(4aS,5S)-1-butyl-octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one
##STR00037##
[0285] 99 mg (109 .mu.mol) polymer bound
(4aS,5S)-octahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(1H)-one are
reacted according to said method with 93 .mu.l (0.87 mmol)
1-bromobutane. The cleavage from the polymer substrate and the
purification are carried out as described above (yellow oil).
[0286] Yield: 18.1 mg, 72 .mu.mol, 66%
[0287] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 0.97 (t, J=6.1
Hz, 3H), 1.04 (s, 3H), 1.11 (s, 3H), 1.20-1.95 (m, 15H), 2.16-2.28
(m, 2H), 2.74 (brs, 1H), 3.13-3.17 (m, 1H).
General Method 7 and 8:
##STR00038##
[0289] The illustrated general method 7 comprises contrary to the
general method 1 the conversion of the carbonyl group at the
position 2 of the hydronaphthalen into a hydroxy group. Via the
obtained OH group the functionalization of these compounds is
achieved on the opposite side of that molecule, i.e. at position 5.
This is carried out according to the general method 3 which is then
followed by the general method 5. The hydroxy group at position 2
can be protected or linked to a solid phase and the chemical
reactions described herein can be applied to the carbonyl group at
position 5.
General Method 9:
##STR00039##
[0291] General method for the Wittig reaction at the solid phase
according to general method 4. Contrary to that method the
conversion of the carbonyl group herein takes place in the 5
position. In the present case, the substituents R.sup.1 and R.sup.2
do not form together a carbonyl group. R.sup.1 and R.sup.2 may form
a carbonyl protecting group such as a dioxolane or a ketal or one
of R.sup.1 and R.sup.2 represents a hydroxy group which is bound to
a solid phase or optionally protected by a hydroxy protecting
group.
General Method 10:
##STR00040##
[0293] General method for the aldol reaction at the solid
phase.
[0294] In this conversion generally referred to as aldol reaction
enolates of aldehydes, ketones, esters or amides react as
nucleophiles with other carbonyl groups as electrophiles. The
enolate is generated from the C,H-acidic carbonyl compound with a
base.
[0295] To a solution of 10 eq. Diisopropylamine in THF (1 ml/mmol)
9 eq. of butyllithium in hexane are added at -78.degree. C. After
the solution is warmed to room temperature it is added to 1.0 eq.
of the loaded resin, which was initially swelled two times with dry
THF for 15 min and washed. It is shaked at room temperature for 30
min and afterwards it is cooled to 0.degree. C. 12 eq. of the
corresponding aldehyde are added, whereupon it is shaked for 30 min
at 0.degree. C. and for 2 h at room temperature. The solvent is
filtered off and the resin is washed three times each with THF,
dichloromethane: methanol=1:1 (v/v), methanol,
dichloromethane:methanol=1:1 (v/v), and dichloromethane. Finally
the resin is dried under vacuum.
Example 10
Synthesis of
(3E,4aS,5S)-3-benzylidene-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethyln-
aphthalen-2(3H)-one (Compound No. 18)
##STR00041##
[0297] 50 mg (55 .mu.mol) of polymer bound
(4aS,5S)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-dimethylnaphthalen-2(3H)-o-
ne are reacted according to this method with 0.10 ml (0.73 mmol) of
diisopropylamine, 0.27 ml (0.66 mmol) of a 2.5 M solution of
butyllithium in hexane and 0.107 ml (1.06 mmol) freshly distilled
benzaldehyde.
General Method 11:
##STR00042##
[0299] According to general method 10 the obtained compound can be
further modified via the Sonogashira reaction at the solid
phase.
[0300] This reaction allows the coupling of terminal alkines with
aryl or vinyl halogenides by means of palladium-copper catalysis
and under use of an amine as base. For the coupling of ethine, even
in the case of an ethine excess, a trimethylsilyl protection group
has to be introduced due to the double sided reaction.
[0301] 1.0 eq. of the dried resin is admixed under argon with 1.0
eq. of CuI, 0.5 eq. of Pd(PPh.sub.3).sub.4, DMF (15 ml/g resin), 20
eq. of diisopropylethylamine and 15 eq. of the corresponding
terminal alkine. Afterwards it is shaked at 90.degree. C. over
night. The solvent is filtered off and the resin is washed three
times each with THF:H.sub.2O=2:1 (v/v),
dichloromethane:methanol=1:1 (v/v), methanol, dichloromethane
methanol=1:1 (v/v), and dichloromethane. Finally the resin is dried
under vacuum.
General Method 12:
##STR00043##
[0303] According to general method 10 the obtained compound can be
further modified via the Heck reaction at the solid phase.
[0304] The Heck reaction allows the C--C coupling between olefins
and aryl or vinyl halogenides under pallasium catalysis.
[0305] 1.0 eq of the dried resin is swelled under argon with DMF
(10 ml/g) for 15 min. Afterwards 5.0 eq. of olefin, 0.2 eq. of
Pd(OAc).sub.2, 2.0 eq. of PPh.sub.3 and 1.5 eq. of
tetramethylethylendiamine are added. The suspension is shaked at
70.degree. C. over night, the solvent is filtered off and the resin
is washed three times each with THF:H.sub.2O=2:1 (v/v),
dichloromethane:methanol=1:1 (v/v), methanol,
dichloromethane:methanol=1:1 (v/v), and dichloromethane. Finally
the resin is dried under vacuum.
Example 11
Synthesis of
(3E,4aS,5S)-3-(4-styrylbenzylidene)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-
-dimethylnaphthalen-2(3H)-one
##STR00044##
[0307] 30 mg of polymer bound
(3E,4aS,5S)-3-(4-iodobenzylidene)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(3H)-one (Compound No. 69) are swelled according
to this method in 2 ml of DMF under argon. Afterwards 17 .mu.l
(0.165 mmol) of styrene, about 1 mg (4.5 .mu.mol) of Pd(OAc).sub.2,
17.3 mg (66 .mu.mol) of PPh.sub.3 and 3.8 mg (33 .mu.mol) of
tetramethylethylenediamine are added. The suspension is shaked at
70.degree. C. over night, the solvent is filtered off and the resin
is washed three times each with THF: H.sub.2O=2:1 (v/v),
dichloromethane: methanol=1:1 (v/v), methanol,
dichloromethane:methanol=1:1 (v/v), and dichloromethane. Finally
the resin is dried under vacuum and it is cleaved and purified as
described above (yellow oil).
[0308] Yield: 9.1 mg, 24 .mu.mol, 72%
[0309] R.sub.f-value: 0.14 (cyclohexane/ethylacetate 3:1 v/v)
[0310] [.alpha.].sub.D.sup.20=+60.degree. (c=1.05, CHCl.sub.3)
[0311] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.24 (s, 3H),
1.27-1.68 (m, 4H), 1.85 (s, 3H), 2.04-2.83 (m, 4H), 3.23 (t, J=7.2
Hz, 1H), 7.10 (d, J=16.3 Hz, 1H), 7.15 (d, J=16.3 Hz, 1H),
7.22-7.45 (m, 10H).
General Method 13:
##STR00045##
[0313] According to general method 10 the obtained compound can be
further modified via the Suzuki reaction at the solid phase.
[0314] The Suzuki reaction is a palladium catalyzed coupling
between organo boronic acids and aryl halogenids.
[0315] 1.0 eq. of the dried resin is swelled under argon with THF
(10 ml/g) for 15 min. Afterwards 2.0 eq. of Na.sub.2CO.sub.3, 0.5
eq. Pd(PPh.sub.3).sub.4 and 2.0 eq. of boronic acid are added. The
suspension is shaked at 60.degree. C. over night, the solvent is
filtered off and the resin is washed three times each with
THF:H.sub.2O=2:1 (v/v), dichloromethane:methanol=1:1 (v/v),
methanol, dichloromethane:methanol=1:1 (v/v), and dichloromethane.
Finally the resin is dried under vacuum.
Example 12
Synthesis of
(3E,4aS,5S)-3-(4-phenylbenzylidene)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-
-dimethylnaphthalen-2(3H)-one
##STR00046##
[0317] 30 mg of polymer bound
(3E,4aS,5S)-3-(4-iodobenzylidene)-4,4a,5,6,7,8-hexahydro-5-hydroxy-1,4a-d-
imethylnaphthalen-2(3H)-one (Compound No. 69) are swelled according
to this method in 2 ml of THF for 15 min under argon. Afterwards 7
mg (66 .mu.mol) of dry Na.sub.2CO.sub.3, 11 mg (16 .mu.mol) of
Pd(PPh.sub.3).sub.4 and 8 mg (66 .mu.mol) of phenylboronic acid are
added. The suspension is shaked at 60.degree. C. over night, the
solvent is filtered off and the resin is washed three times each
with THF:H.sub.2O=2:1 (v/v), dichloromethane:methanol=1:1 (v/v),
methanol, dichloromethane:methanol=1:1 (v/v), and dichloromethane.
Finally the resin is dried under vacuum and it is cleaved and
purified as described above (yellow oil).
[0318] Yield: 7.7 mg, 21.5 .mu.mol, 65%
[0319] R.sub.f-Wert: 0.19 (cyclohexane/ethylacetate 3:1 v/v)
[0320] [.alpha.].sub.D.sup.20=+41.degree. (c=1.02, CHCl.sub.3)
[0321] .sup.1H-NMR (400 MHz, CDCl.sub.3): .delta. 1.22 (t, J=6.7
Hz, 3H), 1.23-2.14 (m, 8H), 1.95 (s, 3H), 3.23 (t, J=7.5 Hz, 1H),
7.15-7.54 (m, 10H).
Materials and Methods:
[0322] Assay protocols for Cdc25A, 11.beta.HSD1, 11.beta.HSD2, and
AChE are described in detain in the publication of Koch M A,
Wittenberg L O, Basu S, Jeyaraj D A, Gourzoulidou E, Reinecke K,
Odermatt A, Waldmann H (Proc. Natl. Acad. Sci. U.S.A. 2004 Nov. 30;
101(48):16721-6) and in Koch M A et al., Proc. Natl. Acad. Sci.
U.S.A. 2005 Nov. 29; 102 (48):17272-7.
[0323] Assays protocols for the other enzymes mentioned herein
(MtPTPA, PP1, VHR, PTP1B) are disclosed in Schweizer R A S,
Atanasov, G A, Frey B M, and Odermatt A, Mol. Cell. Endocrinol.
2003, 212, 41-49 and Barratte, B., Meijer L., Galaktionov K. &
Beach D, Anticancer Res. 1992, 12, 873-880. For determination of
the phosphatase activity, a general phosphatase assay using
para-nitrophenylphosphate was applied.
* * * * *